Effectiveness and Safety of Drugs For Obesity BJM 2022

STATE OF THE ART REVIEW
BMJ: first published as 10.1136/bmj-2022-072686 on 25 March 2024. Downloaded from http://www.bmj.com/ on 29 September 2024 by guest. Protected by copyright.
Effectiveness and safety of drugs for obesity
Kristina Henderson Lewis,1,2 Caroline E Sloan,2,3,4 Daniel H Bessesen,5 David Arterburn6,7
A B S T RAC T
1
Department of Epidemiology
Recent publicity around the use of new antiobesity medications (AOMs) has focused
and Prevention, Wake Forest the attention of patients and healthcare providers on the role of pharmacotherapy
University School of Medicine,
Winston-Salem, NC, USA in the treatment of obesity. Newer drug treatments have shown greater efficacy and
safety compared with older drug treatments, yet access to these drug treatments is
2
Division of General Internal
Medicine, Department of
Medicine, Duke University limited by providers’ discomfort in prescribing, bias, and stigma around obesity, as
School of Medicine, Durham,
NC, USA well as by the lack of insurance coverage. Now more than ever, healthcare providers
must be able to discuss the risks and benefits of the full range of antiobesity
3
Department of Population
Health Sciences, Duke University
School of Medicine, Durham, medications available to patients, and to incorporate both guideline based
NC, USA
4
Margolis Center for Health advice and emerging real world clinical evidence into daily clinical practice. The
Policy, Duke University, Durham,
NC, USA
tremendous variability in response to antiobesity medications means that clinicians
5
Division of Endocrinology, need to use a flexible approach that takes advantage of specific features of the
Metabolism and Diabetes,
University of Colorado School of antiobesity medication selected to provide the best option for individual patients.
Medicine, Aurora, CO, USA
6
Future research is needed on how best to use available drug treatments in real
Kaiser Permanente Washington
Health Research Institute, world practice settings, the potential role of combination therapies, and the cost
Seattle, WA, USA
7
Division of General Internal
effectiveness of antiobesity medications. Several new drug treatments are being
Medicine, University of evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy
Washington, Seattle, WA, USA
Correspondence to: K H Lewis, of obesity is bright.
[email protected]
Cite this as: BMJ 2024;384:e072686
http://dx.doi.org/10.1136/
bmj‑2022‑072686 Introduction The goal of this review is to summarize recent
The prevalence of obesity (defined as a body mass guideline documents, systematic reviews, and
Series explanation: State of the
Art Reviews are commissioned index ≥30) has increased significantly in recent emerging randomized controlled trials and
on the basis of their relevance decades. Although most definitions of obesity are observational studies related to the safety, efficacy,
to academics and specialists based on body mass index, body mass index is now and health outcomes of antiobesity medications,
in the US and internationally.
For this reason they are written
widely acknowledged to be an imperfect measure of to help guide practicing physicians in their clinical
predominantly by US authors. adiposity and should not replace clinical judgment
decision making. We also alert clinicians to
in the assessment of adiposity related health risks.1 2
emerging trends in treatment and major unanswered
Additionally, adjustments of body mass index based
cut points need to be made for some racial and ethnic research questions to help guide conversations
groups. Regardless of its shortcomings for predicting with patients. Two recently published reviews and
individual health, having a body mass index ≥30 is guideline documents have provided a detailed
associated with increased morbidity and mortality summary of the relative efficacy and safety of these
at a population level and for many individuals.3 drug treatments.10 12 We augment these papers by
This association is manifested in large part by the presenting post-approval evidence on antiobesity
increased risk of weight related complications such medication effectiveness and comparative
as type 2 diabetes,4 hypertension,5 obstructive effectiveness in real world settings, and proposing
sleep apnea,6 and degenerative joint disease.7 In future avenues for research. When patients
light of the burden obesity places on human health meet guideline based criteria for consideration
and a growing understanding of the physiologic
of an antiobesity medication, clinicians should
processes underlying weight regulation, scientific
feel comfortable initiating conversations about
organizations including the American Medical
Association, the National Institutes of Health, and antiobesity medications and responding to their
others now recognize it as a relapsing, remitting patients’ questions. In a busy clinical practice,
chronic disease.8-11 Accordingly, modern guidelines conversations about antiobesity medications need to
recommend a long term treatment approach, which be efficient and to touch on several key points that
can include the use of antiobesity medications can drive clinical decision making. Key points that
(AOM). can guide the discussion are listed in box 1.
the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 1

Box 1: Key considerations for providers considering antiobesity medication prescribing
1. Antiobesity medications approved by the Food and Drug Administration are an evidence based adjunct to lifestyle treatment. Antiobesity medications should
be considered a standard tool to help people with obesity to lose weight and keep it off.
2. Because obesity is a chronic disease, like diabetes or hypertension, patients who want to maintain weight loss should understand that antiobesity
medications will likely need to be continued long term, because weight is usually regained after antiobesity medications are discontinued.
3. Many insurance companies in the United States currently do not cover antiobesity medications, so out-of-pocket costs usually play a role in the selection of
antiobesity medication. Clinicians should be prepared to discuss insurance coverage and drug treatment affordability with their patients.
4. Antiobesity medications vary in average effectiveness, cost, and side effect profile. The clinician and patient should together identify which factors are most
important, and tailor prescribing around those priorities.
5. Antiobesity medications can cause a variety of side effects. A useful initial strategy is to prescribe the selected antiobesity medication at a low dose and titrate
upwards based on the weight response and side effects.
6. The initial antiobesity medication selected should be discontinued and replaced with an alternative if the patient does not have ≥5% weight loss in 3-6
months.
7. Antiobesity medications improve several markers of health, including blood pressure, lipid levels, and glycemic control. Among patients with diabetes,
glucagon-like peptide-1 receptor agonists reduce incident cardiovascular events, and one trial has shown reduced cardiovascular events with semaglutide in
patients with pre-existing cardiovascular disease without diabetes.
Epidemiology naltrexone”, “semaglutide”, “liraglutide”,

In 2017-18, 42% of US adults were living with “tirzepatide”, “setmelanotide”, “cagrilintide”,
obesity (body mass index ≥30), with a similar “orforglipron”, “retatrutide”, “pemvidutide”,
prevalence among men and women.13 Obesity “survodutide” “mazdutide”, “danuglipron”,
shows marked racial and ethnic disparities, with “apitegromab”, “taldefgrobep”, and “HU6”. Our
the lowest prevalence among non-Hispanic Asian search was limited to English language articles and
adults (17.4%) and the highest prevalence among focused on drug treatments that are available in the
non-Hispanic black (49.6%) and Hispanic (44.8%) US. Priority was given to evidence obtained from
adults.13 The global prevalence of obesity nearly the most recent systematic literature reviews, meta-
doubled in 70 countries between 198014 and 2015. analyses, and when possible, any subsequently
The Global Burden of Disease study found in 2019 published randomized controlled trials. Where
that roughly 41% of all deaths from metabolic possible, we prioritized studies of at least one year in
diseases were attributable to obesity.15 duration. Patient stakeholders were engaged in the
While public interest in antiobesity medications creation of the manuscript (see box ‘How patients
seems to be increasing rapidly in recent years, were involved in the creation of this article’).
published data on current levels of use are lacking.
Historically, use of antiobesity medications has Current antiobesity medications FDA approved for use
been relatively low compared with the numbers in the US
of eligible patients. In 2012-16, the United States Owing to differences in approval processes for
Government Accountability Office reported that out drug treatments and in the opinions of regulatory
of the estimated 72 million US adults with obesity, bodies across the globe, the array of antiobesity
only 0.9% had been prescribed an FDA approved medications available for prescribing varies
antiobesity medication in any given year.16 Numerous between nations. This review primarily focuses on
studies have reported similarly poor uptake, ranging drug treatments available in the US. Several FDA
from 1-3% both in the US and Europe.17-27 Patients approved antiobesity medication options are now
who report wanting to lose weight, have a history of available for US providers and patients to consider
bariatric surgery, or are enrolled in intensive weight when initiating pharmacotherapy. Table 1 provides
loss programs might be more likely to be prescribed an overview of the efficacy, side effects, costs,
antiobesity medications,16 19 26 but uptake is low and practical considerations of these antiobesity
even in these groups. The high cost of these drug medications, with an emphasis on data from
treatments, many of which are not covered by health meta-analyses and randomized trials. For ease of
insurance in the US, is likely to lead to uneven access description, we have grouped available antiobesity
to them, which could further exacerbate obesity medications according to the year when they were
related health disparities.28 approved by the FDA as treatments for weight loss.
Importantly, although an increased understanding
Methods of obesity physiology has recently led to the
Sources and selection criteria introduction of some highly effective antiobesity
We based this review on articles found by searching medications, a newer antiobesity medication is
PubMed and the Cochrane Library since inception not always inherently better or more effective
through June 2023, using the terms “systematic for a given patient than an older one. Individual
review”, “randomized controlled trial”, “guideline”, heterogeneity in response to these drug treatments
“weight-loss”, “obesity”, “antiobesity medication”, is substantial, and many patients will have a
“obesity pharmacotherapy”, “phentermine”, clinically meaningful response to older antiobesity
“orlistat”, “phentermine-topiramate”, “bupropion- medications.
2 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

Table 1 | Overview of antiobesity medications approved by the Food and Drug Administration
Placebo Proportion
subtracted of patients
Generic name % weight achieving
(year loss 5% weight Cost for
approved, (95% CI) loss at 1 month
approval Mechanism of Route of at 12-24 12-24 Other weight supply, Ideal use case
type*) action administration months months, % loss estimates Side effects Contraindications $† (special benefits)
Phentermine Sympathomimetic Oral; options Unknown Unknown 5-15% total Common: Dry Cardiovascular 5-20 Young or middle
(1959, short amine; increases for daily or weight loss at mouth, insomnia, disease including aged patient with
term use, DEA norepinephrine three times 6 months29-32 constipation, arrhythmia, no cardiovascular
schedule IV) (primarily), daily dosing (uncontrolled anxiety, history of disease history
dopamine, studies) headache; substance and for whom
serotonin in 7.2% average Possible/ use disorder, affordability of
hypothalamic total weight loss rare: elevated hyperthyroidism, drug treatments is
nuclei that at 24 months33 blood pressure, poorly controlled a concern
regulate hunger (observational tachyarrhythmia; hypertension, (Affordability)
cohort) Theoretical: cardiac
32-80% of cardiovascular valvulopathy
patients lose at events such
least 5% over 3 as myocardial
months29 33-37 infarction, stroke
Orlistat Reversible inhibitor Oral; three 3.2 49.712 2.8% Common: Pregnancy, chronic 0-60 Patient for whom
(1999, long of gastric and times daily (95% CI (95% CI 2.4- flatulence, oily malabsorption cost is a concern
term use) pancreatic lipases; ingestion with 2.8-3.5)12 3.2)10 placebo stools, fecal syndrome (eg, but who is not
inhibits absorption meals subtracted % urgency, fecal celiac disease, worried about
of dietary fats weight loss up to incontinence. inflammatory gastrointestinal
4 years Rare/theoretical: bowel disease, adverse effects or is
liver failure previous bariatric adhering to a very
surgery), low fat diet‡
cholestasis (Few
contraindications)
Phentermine- Phentermine: as Oral; once daily 7.9 74.412 7.8-9.8% total Common: Same Same as 100-150 Young or middle
topiramate above; topiramate: dosing (95% CI weight loss at 12 as phentermine phentermine aged patient with
extended GABAergic agent 6.7-9.3)12 months and + paresthesias, + pregnancy no cardiovascular
release (2012, used for epilepsy, 9.3-10.5% total dysgeusia, category X disease history, with
long term use, carbonic anhydrase weight loss cognitive (topiramate); history of migraine
DEA schedule inhibitor at 24 months dysfunction consider avoiding headache and no
IV) (depending on Possible/ in patients risk of becoming
dose)38 39 rare: same as with glaucoma, pregnant
phentermine nephrolithiasis (Migraine
+ glaucoma, prophylaxis)
nephrolithiasis§
Naltrexone- Naltrexone pure Oral; twice daily 4.112 64.612 3.0% Common: Seizure disorder 500 Patient with alcohol
bupropion opioid antagonist. dosing (95% CI (95% CI 2.5- headache, or high risk of use disorder,
sustained Bupropion: weakly 3.0-5.2) 3.5)10 dizziness, seizures; opioid tobacco use
release inhibits neuronal Placebo nausea, vomiting, use; uncontrolled disorder, and/
(2014, long reuptake of subtracted % depression, initial hypertension; or depression
term) dopamine and weight loss at 56 increase in blood hepatic cirrhosis; and no history of
norepinephrine weeks pressure that current or recent hypertension, who
Mechanism leading resolves by 12 (<14 days) use would be willing to
to weight loss not weeks in RCTs. of monoamine take two separate
fully understood Rare: seizure, oxidase inhibitor, pills if cost was a
cholecystitis, pregnancy concern
suicidal ideation (Alcohol use
disorder,
depression,
tobacco cessation)
Liraglutide GLP-1 receptor Subcutaneous 4.7 6412 Average total Common: Family history 1090 Patient with type
(2014, long agonist; acts injection; daily (95% CI weight loss 8.0% nausea, vomiting, of MEN type 2 diabetes whose
term) centrally to 4.1-5.3)12 +/- 6.7 (SD) at 56 constipation 2 syndrome; insurance will
improve satiety weeks40 Possible/rare: personal history of not cover weekly
and slows gastric pancreatitis medullary thyroid injectables
emptying cancer (Type 2 diabetes)
Setmelanotide Melanocortin-4 Subcutaneous Unknown Unknown Average total Common: None 20 904 Individuals with
(2020, long receptor agonist for injection; daily weight loss hyperpigmentation, an approved
term use) monogenic obesity 5-20%, 45-80% injection site monogenic obesity
syndromes achieved a 10% reactions, indication (POMC,
reduction at 1 gastrointestinal PCSK1, or LEPR
year depending upset, headache, deficiency, Bardet-
on gene defect41 sexual adverse Biedl syndrome)
reactions
(Continued)

Table 1 | Continued
Placebo Proportion
subtracted of patients
Generic name % weight achieving
(year loss 5% weight Cost for
approved, (95% CI) loss at 1 month
approval Mechanism of Route of at 12-24 12-24 Other weight supply, Ideal use case
type*) action administration months months, % loss estimates Side effects Contraindications $† (special benefits)
Semaglutide GLP-1 receptor Subcutaneous 11.4 78.112 Average total Common: Family history 1100 Patient with at least
(2021, long agonist; acts injection; once (95% CI weight loss nausea, vomiting, of MEN type 10% weight loss
term use) centrally to weekly dosing 10.3-12.5)12 14.9% at 68 constipation 2 syndrome; clinically indicated,
improve satiety weeks42 Possible/rare: personal history of with cardiovascular
and slows gastric pancreatitis medullary thyroid disease, or
emptying cancer diabetes/insulin
resistance who
cannot take a
phentermine-
containing agent
(Type 2 diabetes;
cardiovascular-
disease;
substantial weight
loss)
Tirzepatide Dual agonist Subcutaneous 11.9 85-91 Average total Common: Family history 1060 Patient with at least
(2023, long to GLP-1 injection; (95% CI depending weight loss nausea, vomiting, of MEN type 10% weight loss
term) and glucose once weekly 10.4-13.4) on dose 15-21% constipation 2 syndrome; clinically indicated
dependent dosing to 17.843 at 72 weeks Possible/rare: personal history and diabetes or
insulinotropic (95% CI (depending on pancreatitis of medullary insulin resistance
polypeptide 16.3-19.3) dose) thyroid cancer who cannot take
receptors; and depending a phentermine
slows gastric on dose containing agent.
emptying (Type 2 diabetes;
substantial
weight loss)
CI=confidence interval; DEA=Drug Enforcement Administration; GABA=γ-aminobutyric acid; GLP-1=glucagon-like peptide-1; MEN=multiple endocrine neoplasia; RCT=randomized controlled trial;
SD=standard deviation.
*Short term indicates three months; long term indicates 12 months or longer.
†In US dollars, 2023 reported average wholesale prices (does not account for potential insurance coverage).
‡Also recommended to prescribe a daily multivitamin with orlistat owing to resulting malabsorption of fat soluble vitamins.
§In clinical trials, no difference in serious adverse event rate was observed for active drug participants compared with placebo.
Antiobesity medications approved before 1999 2014. These drug treatments are dosed daily or more
The group of antiobesity medications approved frequently, and provide a wide range of average weight
before 1999 which are still available on the market is loss, as low as 3% and up to 11% depending on dose
small and includes phentermine and the other older and duration of use. Importantly, two of the antiobesity
sympathomimetic amines (eg, phendimetrazine). medications in this category represent combinations
Having been available on the market for over half a of drug treatments which, when used alone in an off-
century, phentermine is currently the most widely label fashion, can independently promote weight loss.
prescribed antiobesity medication in the US because of Topiramate, for example, was previously studied as a
its low cost; however, long term data to guide outcome standalone antiobesity medication, but formal FDA
comparisons with newer antiobesity medications approval for weight management was never sought.
are almost completely lacking. Of note, unlike newer The doses used in the initial trials of topiramate
antiobesity medications, phentermine is only FDA monotherapy were as high as 192 mg daily and
approved for three months of use, although recent produced 6-8% placebo subtracted weight loss in
guideline documents do provide guidance for longer patients with obesity.44-46 In a 48 week clinical trial of
term prescribing (as summarized later). bupropion monotherapy 300-400 mg daily for patients
with obesity, the average weight loss in patients was
Antiobesity medications approved from 1999 2.4-3.2% higher than placebo.47 48
to 2014
This group of antiobesity medications have varying Antiobesity medications approved in 2015 or later
mechanisms of action, reflecting an evolving This group of antiobesity medications, which includes
understanding of obesity physiology during the period. those currently awaiting approval, contains highly
The group includes orlistat, which blocks dietary fat effective drug treatments (mean weight loss 11-21%)
absorption and was approved in 1999, the combination that primarily target incretin pathways such as the
of phentermine and topiramate extended release GLP-1 receptor agonist semaglutide (approved for
approved in 2012, the combination of naltrexone obesity in 2021), and the novel combination GLP-1
and bupropion, and the glucagon-like peptide (GLP- receptor agonist/glucose dependent insulinotropic
1) receptor agonist liraglutide, both approved in polypeptide (GIP) receptor agonist tirzepatide

(approved for obesity in 2023). In their current Antiobesity medications developed for the
formulations, these drug treatments (semaglutide treatment of genetic syndromes resulting in obesity
and tirzepatide) are injected weekly, and in placebo The only drug treatment currently in this final
controlled clinical trials, resulted in greater weight category is setmelanotide. This agent is not approved
loss than was seen with older antiobesity medications. for treatment of general obesity but is specifically
They are also substantially more expensive than older useful in monogenic and syndromic obesity.
antiobesity medications. Several additional highly
effective antiobesity medications and combinations Overview of non-FDA approved options for obesity
that leverage nutrient sensitive hormone pathways pharmacotherapy
are in late phase clinical trials, and will likely become Several drug treatments that are not specifically
available over the coming years. These antiobesity approved by the FDA as antiobesity medications
medications include oral versions of GLP-1 receptor have been found to cause weight loss in some people
agonists, which could be important for patients who (table 2). Here, we summarize the existing evidence
are hesitant to use injectable drug treatment. around weight loss efficacy and safety considerations
Table 2 | Overview of selected drug treatments used in an off-label fashion for weight loss
Placebo Proportion
subtracted % of patients
weight loss achieving Cost for
(95% CI) 5% weight 1 month
Generic name or Mechanism of Route of at 12-24 loss at 12-24 Other weight supply, Ideal use case
class action administration months months, % loss estimates Side effects Contraindications $* (special benefits)
Metformin Multiple Oral; options 2.5 43.212 Common: nausea, Renal dysfunction; 11-50 Patients with
mechanisms, for daily or (95% CI, vomiting, diarrhea decompensated diabetes or pre-
including AMPK twice daily 1.7-3.3) Possible/rare: congestive cardiac diabetes
dependent dosing in patients lactic acidosis in failure; acute or (Polycystic ovary
and AMPK with pre- people with heart chronic metabolic syndrome)
independent diabetes or failure, kidney acidosis; impaired
mechanisms diabetes12 or liver disease, hepatic function
alcohol use
disorders
Topiramate GABAergic Oral; options 2.4-8.0 at 36-67 10% weight loss Common: Pregnancy category 3-244Patients with
agent used for daily or 6 months achieved by 29- paresthesias, X; consider history of migraine
for epilepsy, twice daily depending 44% of patients, dysgeusia, avoiding in patients headache or on
carbonic dosing on dose and depending on cognitive with glaucoma, antipsychotics
anhydrase study49 50 dose dysfunction nephrolithiasis and no risk of
inhibitor Possible/ becoming pregnant
rare: glaucoma, (Migraine
nephrolithiasis prophylaxis;
antipsychotic
induced weight
gain)
Bupropion Weakly inhibits Oral; options 2.8-3.2 in 40 Common: Seizure disorder or 17-230 Patient with
neuronal for daily or patients headache, dry high risk of seizures; tobacco use
reuptake of twice daily with major mouth, insomnia, uncontrolled disorder and/or
dopamine and dosing depression51 tachycardia, hypertension; depression and no
norepinephrine. at 26 weeks tremor, hepatic cirrhosis; history
Mechanism hypertension current or recent (Depression,
leading to Rare: seizure, (<14 days) use of tobacco
weight loss not suicidal ideation monoamine oxidase cessation)52
fully understood inhibitor
SGLT2 inhibitor Reduces renal Oral; daily 2.1 51.1 Common: nausea, Severe renal 300- Patients with
drug treatments tubular glucose dosing (95% CI, fatigue, polyuria, dysfunction 500 diabetes and
(canagliflozin, reabsorption, 1.1-3.0) in polydipsia, and heart failure who
dapagliflozin, and producing a patients with xerostomia might have mild
empagliflozin) reduction in diabetes Possible/rare: to moderate renal
blood glucose acute renal injury dysfunction
without (Safe for use
stimulating in patients
insulin release with mild to
moderate renal
dysfunction)
Lisdexamfetamine Blocks the Oral; daily Unknown Unknown Average total Common: Monoamine oxidase 100- Patients with
reuptake of dosing weight loss in Decreased inhibitor use 400 obesity and binge
norepinephrine patients with appetite; headache eating disorder or
and dopamine; binge eating nausea; upper ADHD
primary disorder 3.1-4.3 abdominal or (ADHD treatment)
approval for kg at 11 weeks53 stomach pain;
ADHD treatment vomiting
ADHD=attention deficit hyperactivity disorder; AMPK=adenosine monophosphate activated protein kinase; CI=confidence interval; GABA=γ-aminobutyric acid; SGLT2=sodium glucose
cotransporter 2.
*In US dollars, 2023 reported average wholesale prices (does not account for potential insurance coverage).

for some of these options. As noted above, guidelines efficacy.57-59 Longstanding bias and stigma towards
generally recommend against the off-label use of patients with obesity is probably an important
these drug treatments exclusively for weight loss contributing factor as well. Providers might think
purposes. that obesity represents a failure of character and that
prescribing antiobesity medications is giving patients
Metformin the “easy way out.” Patients can have internalized
Metformin is a generic biguanide agent commonly stigma, blame themselves for their weight, and even
used to treat type 2 diabetes, but it can also lead to avoid healthcare altogether60-65 (table 3).
modest weight loss (eg, 2.5% more than placebo).12 54
Metformin is best used in patients with type 2 diabetes, Observed effectiveness of antiobesity medication in
pre-diabetes, or polycystic ovarian syndrome who are real world settings
unable to tolerate or afford a GLP-1 receptor agonist. Most studies evaluating the real world effectiveness
of FDA approved antiobesity medications are
single arm retrospective observational studies that
Sodium glucose cotransporter 2 (SGLT2) inhibitors
compare post-drug treatment weights with pre-drug
SGLT2 inhibitors are drug treatments that are FDA
treatment weights.75 79 Two thirds of these studies
approved for use in patients with type 2 diabetes,
were conducted in specialty weight management
heart failure, and chronic kidney disease. They
clinics or centers, where access to and knowledge of
are associated with modest weight loss (eg, 2.1%
antiobesity medications is typically higher than in
more than placebo).12 SGLT2 inhibitors could be
primary care settings. The majority were conducted
particularly useful in patients with heart failure, for
in the US. Most of these studies were aggregated in
whom phentermine is contraindicated. Metformin
two reviews published in 2021.75 79 Twenty nine
can also be useful in patients with decompensated
additional studies have since been published.80-108
heart failure. In patients with diabetes, the glucose
In general, the efficacy of antiobesity medications
lowering properties of SGLT2 inhibitors could also
persists in real world scenarios across many different
help reduce doses of insulin, a known contributor to
groups of patients; however, estimated weight loss is
weight gain. Side effects of SGLT2 inhibitors include
highly variable between studies, even within a single
genitourinary tract infections and urinary frequency.
antiobesity medication. In three long term studies
evaluating the effectiveness of taking any antiobesity
Lisdexamfetamine medication at any dose, weight loss was 2.2-9.3% at
Lisdexamfetamine is an amphetamine derivative, 12 months and 10.5% at 24 months.83 84 109 A common
FDA approved for binge eating disorder and attention finding was that patients experienced greater weight
deficit hyperactivity disorder, and is associated with loss when they consistently took their prescribed
modest weight loss.55 Lisdexamfetamine might antiobesity medications. However, many patients stop
be a preferred treatment for adults with obesity using antiobesity medications over time owing to lack
and binge eating disorder. Importantly, this is of effectiveness, side effects, or difficulty obtaining
a Drug Enforcement Administration schedule II them because of inadequate insurance coverage and
drug treatment (high potential for abuse), which high cost.75 Long term efficacy estimates in real world
has implications for restrictions on prescribing. settings could reflect a selection for those patients
Additionally, based on its mechanism of action, who find the drug treatments useful and are able to
lisdexamfetamine has similar cardiovascular acquire them consistently.
contraindications to phentermine.
Phentermine
Antiobesity medication use in practice: current patterns Most studies evaluating the effectiveness of
of use and real world evidence on effectiveness phentermine in clinical practice have followed
Rates of antiobesity medication prescriptions tend to patients for only three months.29 34 110-116 Total
be specific to the clinician and the site of practice, with percentage weight loss in these studies was widely
a subset of clinicians and certain sites prescribing divergent, ranging between 2.1-12.8%,29 34 111-
a majority of antiobesity medications.19 20 56 113 115
and similarly, estimated rates of clinical
For example, in 2010, antiobesity medication response (proportion of patients experiencing
prescription rates for US veterans with obesity ranged ≥5% weight loss) were also broad, ranging from
from 0-21% of eligible patients across 140 Veterans 21-97%.29 34 110 111 114 Limited observational data
Health Administration facilities nationwide.19 suggest that patients who remain on phentermine
Clinicians who do prescribe antiobesity medications for longer than three months are generally able to
appear to frequently do so in an off-label fashion, with, maintain their weight loss. In a study of 13 972 US
for example, up to half of phentermine prescriptions patients with obesity who took phentermine for up to
lasting >3 months and one third lasting >1 year.20 In two years, those who consistently took phentermine
surveys, physicians and advance practice providers for ≥1 year had an average weight loss of 7.5% two
describe several major barriers to prescribing years after initiation.33
antiobesity medications, including high costs and
lack of insurance coverage, side effects, medication Naltrexone-bupropion
interactions, insufficient knowledge, lack of time In a single large study evaluating the effectiveness of
for weight loss counseling, and a perceived lack of naltrexone-bupropion in multiple US primary care

Table 3 | Barriers to evidence based prescribing of antiobesity medications in clinical practice
Barrier Pertinent data Possible solutions
Cost of drug • Insurance coverage of antiobesity medications in the US is highly variable and is not required by law.66-69 • Drug prices are expected to fall as additional
treatments, • In 2015-2016, among 7378 adults surveyed about their employer based insurance, 21% reported highly effective antiobesity medications
limited having coverage for antiobesity medications.66 enter the market in the coming years.
insurance • As of 2017, only 16 out of 50 state Medicaid plans cover ≥1 antiobesity medication.68 Medicare Part D • Prices will fall further as the drugs come off
coverage, and does not cover treatment with any FDA approved antiobesity medications at all. patent and become available as generics.
supply chain • The GLP-1 receptor agonists liraglutide and semaglutide are particularly expensive, costing $324- Liraglutide is expected to come off patent
problems 1619/month before insurance.70 71 within the next five years.
• No consensus exists on the healthcare cost impact of long term antiobesity medication use. Different • States, payers, and employers are
studies have used various assumptions, with some estimating substantial savings in healthcare costs, increasingly considering and expanding
while others estimate a net cost increase.69 72 coverage for antiobesity medications
• Shortages in availability of newer medications have made it difficult to initiate and consistently
maintain patients on these treatments as they are first coming to market73
Concerns about • Clinicians’ concerns about side effects59 might be related to the recall of several antiobesity medications • Ongoing clinical trials investigating
safety of long owing to increased risk of valvular heart disease and pulmonary hypertension (fenfluramine), stroke and cardiovascular outcomes and longer term
term antiobesity myocardial infarction (sibutramine), and cancer (lorcaserin).74 safety of antiobesity medications will likely
medication use • In real world effectiveness studies of currently approved antiobesity medications, most adverse events help reduce concerns.
are reported as mild and moderate. That said, how frequently side effects are severe enough to lead to • Additional postmarketing surveillance studies
discontinuation is unclear from these studies.75 will likely be conducted in the coming years
• Long term safety of antiobesity medications outside of clinical trials is not well understood75 76
Lack of clinician • Primary care physicians’ knowledge of obesity guidelines is poor. In one survey of 1506 primary care • Educational interventions that aim to improve
awareness/ physicians, only 8% could correctly identify guideline recommended weight and weight loss criteria for clinical knowledge of obesity and its treatment
education starting and continuing antiobesity medications77 options have been shown to increase comfort
with counseling about and prescription of
antiobesity medications.78
Antiobesity • Implicit and explicit bias against people with obesity is widespread among physicians, nurses, students, • Various groups are developing interventions
stigma and bias and nutritionists,62-64 owing to a belief that obesity is primarily caused by poor behavior. and trainings for healthcare providers to help
• Even obesity specialists who were surveyed at an obesity related medical conference in 2013 revealed identify and mitigate bias and stigma
implicit and explicit bias, pairing words like “bad” and “lazy” with “obese.”65 These biases have real
implications for the care that patients receive. For example, clinicians perceive patients with higher
body mass index to have lower drug treatment adherence,61 and therefore, could be reluctant to
prescribe antiobesity medications.
• In audiorecorded visits, clinicians provide less empathy, legitimation, and reassurance to patients with
overweight and obesity60
FDA=Food and Drug Administration; GLP-1=glucagon-like peptide-1.
and specialty clinics affiliated with an academic Semaglutide

medical center, at three months, the observed The effect of semaglutide on weight loss has also been
percentage weight loss was 2.7%, and 29% of evaluated as a secondary outcome in observational
patients had achieved ≥5% weight loss.112 studies among patients with type 2 diabetes,95-105 107 108
where the primary outcome was HbA1c. Among studies
Orlistat reporting this outcome, percentage weight reduction
In 13 observational studies conducted on four ranged from 2.2-7.5% over 9-18 months of follow-
continents,34 80 117-126 percentage weight loss with up.95-108 Only one retrospective study has evaluated
orlistat ranged from 2.2-5.0% at three months34 121 123 weight loss as a primary outcome among patients with
and 4.6-10.7% at six months.34 118 120-122 The obesity without type 2 diabetes. This study94 used
proportion of patients achieving ≥5% weight loss electronic health record data at one academic health
in these studies was 22-38%121 123 at three months, system to evaluate 175 patients with obesity who took
with more variability in this metric at six months semaglutide for ≥3 months. Mean weight loss was
(14-51%).118 124 5.9% at three months and 11% at six months. The
proportion of patients achieving ≥5% weight loss was
Liraglutide 54% at three months and 55% at six months. Weight
In 17 observational studies evaluating liraglutide’s loss was significantly lower among patients with type
real world effectiveness across North America, East 2 diabetes, consistent with findings from clinical trials.
Asia, Europe, and the Middle East,80 82 85-92 127-133 Only 3% of patients discontinued the drug owing to
percentage weight loss ranged from 4.8-9.2% at 4-6 gastrointestinal side effects. Of note, 148 out of 408
months85 87 88 90-92 129 130 132 133; the proportion of patients who were initially prescribed semaglutide
patients achieving ≥5% weight loss was 32-44% at were excluded from the study because they could not
three months130 and 40-65% at six months.86 127 129 access the drug treatment, owing to either insurance
Adherence to liraglutide in real world studies denials or pharmacy shortages.
is generally higher than to other antiobesity
medications,80 85-88 90-92 127-132 134 although direct Comparative effectiveness studies
comparisons are difficult to make because of Randomized trials
variation in the ways adherence was measured Because of their high financial and time costs,
across studies. limited evidence has been published to date from

randomized trials comparing the effectiveness of included intensive lifestyle intervention, orlistat,
different antiobesity medications head-to-head. phentermine, phentermine-topiramate, lorcaserin,
One trial of 338 adults with overweight or obesity liraglutide, and semaglutide.142 Phentermine was
and without type 2 diabetes found that once weekly found to be the most cost effective strategy, followed
subcutaneous semaglutide resulted in significantly by semaglutide, with all other treatment options
greater weight loss at 68 weeks compared with once being dominated by these options (more effective
daily subcutaneous liraglutide135 (-15.8% with and cheaper). Finally, another model found that
semaglutide v -6.4% with liraglutide (difference -9.4 phentermine-topiramate in addition to lifestyle
percentage points (95% confidence interval -12.0 modification was the most cost effective option,
to -6.8), P<0.001)). These findings are consistent particularly when prescribed generically.143 The
with other randomized trials of patients with type 2 model also reported that, at current prices in the US,
diabetes,136-138 where patients receiving semaglutide the cost effectiveness of semaglutide or liraglutide in
had better improvement in weight and HbA1c than patients without type 2 diabetes exceeded commonly
those receiving liraglutide. Another randomized trial used cost effectiveness thresholds. The health benefit
including 756 adults found that the combination price benchmark for semaglutide (defined as the
phentermine-topiramate 7.5 mg/46 mg (-8.5%) price range that would achieve incremental cost
and 15 mg/92 mg (-9.2%) achieved greater weight effectiveness ratios between $100 000 and $150
loss versus placebo (P<0.0001) and their respective 000 per QALY gained), was estimated at $7500 to
monotherapies (P<0.05) at 28 weeks.139 $9800 per year, which would require a discount from
the wholesale acquisition cost of 44-57%. Given
Network meta-analyses the variability in modeling approaches used across
A systematic review and network meta-analysis studies and the strong assumptions necessary to
(search date March 2021) identified 143 trials that conduct these models, further research is necessary
enrolled 49 810 participants.12 The main findings before firm conclusions can be drawn about the most
were that placebo subtracted percentage weight loss cost effective approach to prescribing antiobesity
was highest with phentermine-topiramate (-7.97%; medication.
95% confidence interval -6.7 to -9.3) and GLP-1
receptor agonists (-5.8%; -5.2 to -6.3). In a post hoc Remaining gaps in evidence and call to action for future
analysis that separated the GLP-1 receptor agonists, research
percentage weight loss was higher for semaglutide Personalized treatment approaches to antiobesity
(-11.4%; -10.3 to -12.5) than for liraglutide medication prescribing
(-4.7%; -4.1 to -5.3). Phentermine-topiramate and As is true with other forms of obesity treatment,
naltrexone-bupropion had the highest risk of adverse patient response to antiobesity medications is
events leading to discontinuation. A recent analysis highly variable. Ideally, clinicians would select
of SURMOUNT-1 and STEP 1 trial data concluded the antiobesity medication most likely to lead to
that tirzepatide was likely more effective than clinically significant weight loss in a given patient.144
semaglutide.140 The choice is easy in patients with specific forms of
monogenic or syndromic obesity where setmelanotide
Real world comparative effectiveness data is uniquely beneficial.145 Unfortunately, the
We found insufficient data from observational published research is not sufficient to accurately
comparative effectiveness research designs to predict individual response to antiobesity
understand the real world treatment effectiveness and medications. However, several principles can be
safety of antiobesity medications.80 More research used in clinical practice to make an initial selection
is needed to help inform treatment decisions in of antiobesity medication. First is a consideration
populations that are not typically included in clinical of how secondary effects of drug treatments might
trials, such as those with multiple comorbidities and be beneficial to individual patients (table 1). For
advanced age. example, naltrexone-bupropion might be preferred
for a patient with depression, binge eating, or food
Cost effectiveness studies cravings.146 147 Phentermine-topiramate extended
Cost effectiveness analyses use modeling strategies release might be useful in patients who have another
to estimate the value of alternative treatment indication for topiramate, such as peripheral
strategies and relate them on a cost per quality neuropathy or migraine headaches. GLP-1 receptor
adjusted life year (QALY) scale. A cost effectiveness agonists are particularly useful in people with type 2
analysis comparing semaglutide 2.4 mg weekly diabetes. Some evidence suggests that phentermine
with three other antiobesity medications (liraglutide might be more effective in people who eat excessively
3 mg, phentermine-topiramate, and naltrexone- owing to hunger (as opposed to emotional stress,
bupropion)141 found that semaglutide 2.4 mg was cost boredom, etc).148 While clinicians can and do use
effective compared with all other comparators, with these generalizations, few studies have specifically
the incremental cost per QALY gained ranging from evaluated the effectiveness of antiobesity medication
$23 556 to $144 296. A separate model compared in these subpopulations.
costs and outcomes of seven weight loss strategies Another important question for healthcare systems
plus no treatment for five years. The treatments is how to balance effectiveness and cost, given the

large number of people who could potentially benefit agent targeting a different pathway be started? These
from antiobesity medications. Newer antiobesity are critical questions that should be answered as
medications reliably produce more weight loss than part of future research priorities on antiobesity
older drug treatments, but they cost substantially medications.
more. It might not be financially viable in the short
term to provide insurance coverage for the newest, Weight loss maintenance
most effective drug treatments for all eligible patients. Another unanswered question in obesity medicine is
Therefore, it could be seen as reasonable to use the how best to manage antiobesity medications during
older, less expensive drug treatments in patients with weight loss maintenance. Increasingly, clinical trials
lower body mass index or those without extensive of antiobesity medications follow patients up to 2-3
comorbid conditions. Since some individuals will years after initiation of a drug treatment, and have
have an excellent response to older drug treatments, provided strong evidence that clinically significant
it could also be reasonable to try these first, and weight loss is maintained so long as patients stay on
reserve newer, more effective drug treatments for the drug treatment.38 Following a 20 week run-in on
those who are “non-responders” to older drug semaglutide, the STEP 4 trial randomized participants
treatments and/or need more weight loss for health to remain on study drug versus placebo until week
benefits. For example, patients with a lower body 68. Those who remained on active drug lost an
mass index might not need the 15% or 20% weight additional 8% of their body weight, while those on
loss that are more likely to be produced by newer drug placebo regained 7%, for a final difference between
treatments. Current guidelines have focused broadly groups of 15% body weight.156 Thus, much as has
on which patients should be offered treatment for been observed for lifestyle interventions,157 weight
obesity. A consensus on weight loss targets has not regain seems a foregone conclusion for patients
yet emerged, other than an established minimum of who discontinue obesity treatment, including
5% weight loss. antiobesity medications. Guidelines recommend
the long term use of antiobesity medication, yet the
Combination therapy practical, clinical, and economic implications of this
In light of the multiple neuroendocrine pathways recommendation are unknown. In particular, the
governing body weight and appetite,11 a single agent long term safety implications of taking these drug
pharmacotherapy approach is likely inadequate to treatments beyond a few months to a few years are
support durable, clinically significant weight loss for not yet known. Long term safety is an important
all patients. In a nod to this idea, current antiobesity area for future research, especially as antiobesity
medications in the pipeline include dual agonist medication use is increasing among young adults
and triple agonist agents, drugs that simultaneously and even adolescents. Additionally, with an average
target multiple pathways (eg, tirzepatide, which wholesale price of $1619 to $2023 per month,158
targets GLP-1 receptor agonist and GIP receptor the indefinite use of semaglutide for all but the most
agonist)43 in an attempt to circumvent these natural economically advantaged patients would present an
redundancies.149-152 enormous financial strain under current payment
Whether currently available (and possibly generic, models.159 Substantial changes to the way payers
more affordable) agents might be combined in a cover these drug treatments, and/or major reductions
stepwise, off-label fashion to produce greater total in price for the drugs by pharmaceutical companies,
weight loss or more durable weight loss has not could make the widespread long term use of GLP-1
been rigorously studied. Given a lack of research receptor agonists and similar drugs more feasible in
on this topic, modern obesity treatment guidelines the future.
state that, while promising, off-label combination Key research and policy questions that must be
therapy is not recommended.153 By contrast, modern resolved moving forward include whether more
treatment guidelines for type 2 diabetes154 and affordable (albeit likely less efficacious) antiobesity
essential hypertension155 (also nutrition related medications, a cycling on/off approach, or a lower
chronic diseases), do recommend a stepped care dose antiobesity medication could be used for
approach to pharmacotherapy. In some cases, weight loss maintenance; and if so, when best
guidelines even recommend starting combination to initiate a trial of these strategies, and in which
therapy as an initial approach to facilitate the more patients.
rapid achievement of glycemic or blood pressure
targets. Outcomes beyond percentage weight loss
In practice, the lack of a clear guideline around Historically, one challenge to broader uptake
combination therapy for obesity presents a of antiobesity medications has been the lack of
conundrum: how should providers manage a patient randomized trial evidence showing that these
who had an initial clinically significant response to treatments reduce adverse health outcomes.
a single agent (eg, liraglutide), but has subsequently Recently, however, the SELECT trial reported a 20%
plateaued or begun to regain weight after longer reduction in the risk of cardiovascular events with
term exposure? Should the agent be discontinued in semaglutide 2.4 mg versus placebo over a mean
favor of another; or, similarly to how we approach duration of treatment of 34 months among 17 604
hypertension or type 2 diabetes, should an additional patients 45 years of age or older who had pre-existing

cardiovascular disease and a body mass index of 27 Tirzepatide is currently approved for use in type 2
or greater but no history of diabetes.160 A primary diabetes and obesity. Weight loss with tirzepatide
cardiovascular endpoint event occurred in 569 of the is being evaluated in the SURMOUNT studies.
8803 patients (6.5%) in the semaglutide group and in SURMOUNT 1 tested tirzepatide at 5, 10, or 15 mg
701 of the 8801 patients (8.0%) in the placebo group weekly for 72 weeks, and found that the 15 mg
(hazard ratio 0.80; 95% confidence interval 0.72 to formulation produced a 17.8% placebo subtracted
0.90; P<0.001). Adverse events leading to permanent weight loss, and 56.7% achieved >20% weight
discontinuation of the trial product occurred in 1461 loss.167 SURMOUNT 2 tested tirzepatide in people
patients (16.6%) in the semaglutide group and 718 with type 2 diabetes, and at 72 weeks found a slightly
patients (8.2%) in the placebo group (P<0.001). lower (11.5%) placebo subtracted weight loss.168
Another recent study showed that semaglutide In SURMOUNT 3, subjects who lost >5% with an
2.4 mg resulted in improvements in symptoms intensive lifestyle intervention were randomized to
and walking time in people with heart failure and placebo, 10 mg, or 15 mg tirzepatide weekly. After 72
preserved ejection fraction161 and another analysis weeks, the placebo subtracted weight loss in the 15
showed a reduction in the risk of developing type mg group was 19.9%, with a total placebo subtracted
2 diabetes.162 Additional studies are needed to weight loss including the lifestyle intervention of
investigate the impact of antiobesity medications 22.8%.169
on other weight related health outcomes, such as Evidence of the effectiveness of tirzepatide has
non-alcoholic fatty liver disease and cancer. Another encouraged the development of other dual agonists,
ongoing trial is looking at cardiovascular outcomes including three GLP-1 receptor agonist/glucagon
of tirzepatide, with results expected in the next 1-2 dual agonists: mazdutide (IBI362 or LY3305677),170
years. survodutide (BI456906),171 pemvidutide (ALT-
Along with this line of research, there might need 801), and cotadutide.172 The fact that multiple large
to be a shift in the view of how we define success pharmaceutical companies from the US, Europe,
for a patient following antiobesity medication Japan, and China all have dual agonists in late phase
prescribing. The threshold for clinically significant 2 and early phase 3 programs suggests that dual
response to antiobesity medication has traditionally agonists will be a competitive segment of the market,
been narrowly defined as 5% weight loss at three and gives hope for a range of treatment options and
months after initiation11; however, this goal might lower prices in the future.
not be appropriate for all patients. For example, Retatrutide is the first triple agonist with activity
weight stability and improvement in HbA1c could directed at GLP-1, glucagon, and GIP receptors.172
be a reasonable clinical goal after initiating an Recent phase 2 trial data on retatrutide administered
antiobesity medication in a patient with pre-diabetes at doses of 1-12 mg weekly for 48 weeks showed a
who was previously gaining weight. Similarly, weight placebo subtracted weight loss ranging from 6.6-
stability and improved appetite control in a post- 22.1%.173 In this study, 48% of participants on the
bariatric patient trying to maintain surgical weight highest dose lost >25% of baseline weight and 26%
loss could also be a clinically significant outcome lost >30%. SAR441255 is another triple agonist
from initiating antiobesity medication therapy. currently in early human trials.174
Pramlintide is an amylin analog that is FDA
Emerging treatments approved for the treatment of type 2 diabetes,
The arrival of semaglutide and tirzepatide is just and was studied but never FDA approved as an
the beginning of what promises to be a growing antiobesity medication. A newer long acting acylated
armamentarium of highly effective antiobesity amylin analog named cagrilintide has been studied
medications. Many drugs in the pipeline are based on alone and in combination with semaglutide for the
incretin hormones which have been found to be useful treatment of obesity. In a study of patients with
in the management of type 2 diabetes.163 While most overweight or obesity, the combination of cagrilintide
GLP-1 receptor agonists have been given by injection, 4.5 mg plus semaglutide 2.4 mg per week produced
a number of newer agents can be delivered orally. a 15.4% reduction in body weight at 20 weeks.152
A 50 mg oral formulation of semaglutide recently That study had no placebo arm, and participants
was shown in a phase 3 trial to produce a 12.7% were instructed not to change their diet or physical
placebo subtracted weight loss from baseline to week activity. In a more recent study in subjects with type 2
68.164 Recent phase 2 data on orforglipron, an oral diabetes, this combination produced a 15.6% weight
non-peptide GLP-1 receptor agonist given at doses loss at 32 weeks. This study also had no placebo
ranging from 12-45 mg/day, produced 7.1-12.4% group.175
greater weight loss than placebo at 36 weeks.165 The large weight losses seen with newer highly
Danuglipron is another oral small molecule GLP-1 effective antiobesity medications have raised
receptor agonist that is undergoing phase 2 trials for concerns about the potential for a loss of lean body
the treatment of both obesity and type 2 diabetes.166 mass. Results from the STEP 1 trial of semaglutide
Tirzepatide is the first approved dual agonist. suggested that 40% of total weight loss was derived
Dual agonists are single peptide molecules that from lean mass.42 In response to this concern, new
contain domains conveying receptor agonism for drug treatments are being examined that could help
two different receptors, in this case GLP-1 and GIP. to maintain lean body mass in the context of weight

loss therapy. Several agents acting in the myostatin/ (eg, 3-6 months) owing to lack of durable health
activin A pathway, which regulates skeletal muscle benefits. In 2020, Canada issued its own obesity
mass, are being tested with this goal in mind. treatment guidelines which have since been replicated
Bimagrumab, a monoclonal antibody that blocks the in other countries.178 The Canadian guidelines
activin type II receptor, is administered by infusion primarily differ from US based documents in that
every four weeks. A 48 week trial of bimagrumab recommended antiobesity medication options do
treatment in subjects with obesity and type 2 diabetes not include phentermine or phentermine containing
produced 6.5% overall weight loss, but with a small compounds, which are unavailable in that country.
increase in lean mass.176 Additional agents with Finally, in 2022, the American Gastroenterological
related mechanisms of action that are in the drug Association published the most recent guidelines on
development pathway (phase 2 or earlier) include the pharmacotherapy of obesity.10 These guidelines
apitegromab, taldefgrobep, and the mitochondrial are the first to make priority recommendations for
uncoupling agent HU6. Whether and when these antiobesity medication selection on the basis of
agents will progress to approval for broad use in available evidence from individual agent trials,
patients with obesity is not yet clear. explicitly recommending the use of semaglutide
Many other drug treatments that make use of other 2.4 mg because of the magnitude of clinical benefit.
mechanisms are in preclinical and phase 1 testing, The American Gastroenterological Association
suggesting that this is only the beginning of a period guidelines next prioritize liraglutide 3.0 mg, followed
of remarkable growth in antiobesity medications. by phentermine-topiramate, and then naltrexone-
Unfortunately, very few of these new agents are bupropion. Like the Endocrine Society, the American
currently being tested in children and adolescents. Gastroenterological Association guidelines also allow
for off-label long term phentermine prescribing,
Guidelines while acknowledging the low quality of evidence in
Over the past decade, several professional societies this space. Importantly, they advise against the use
and even nations have issued clinical guidelines that of orlistat as an antiobesity medication, given the
directly deal with the use of antiobesity medications. modern available options that are superior and better
In 2013, The Obesity Society, the American Heart tolerated. A summary approach to prescribing FDA
Association, and the American College of Cardiology approved antiobesity medications based on existing
together issued a comprehensive obesity treatment guidelines is provided in figure 1.
guideline document.177 While expansive in detail It should be noted that, given the expanding
on lifestyle interventions and bariatric surgery, this array of available antiobesity medication options,
document was limited with respect to antiobesity treatment guidelines from just 5-10 years ago are
medications. An expert recommendation was made already becoming out of date. Most reviews on adult
for when to initiate antiobesity medications, stating antiobesity medications from high profile groups
that FDA approved antiobesity medications could be are also out of date, and do not reflect the available
considered as adjunctive treatment for adult patients evidence on the most recent antiobesity medication
with body mass index ≥30 or ≥27 with a weight options.179-182 With more antiobesity medications in
related comorbidity, who were unable to lose weight the pipeline targeting novel pathways, more frequent
or sustain weight loss with lifestyle intervention updates to clinical guidance documents are needed
alone. Additionally, it was recommended to consider to ensure safe and equitable antiobesity medication
discontinuation of antiobesity medications in prescribing. Additionally, evidence synthesis groups
patients not losing at least 5% of their body weight like Cochrane and USPSTF have an important role,
after 12 weeks of treatment. In 2015, following as they can more regularly revise systematic reviews
FDA approval of two new antiobesity medications and meta-analyses as new trial results are published.
for long term use, the Endocrine Society released
its own guidelines outlining the same antiobesity Conclusions
medication initiation criteria as earlier guidelines, Obesity is a serious and growing public health problem
but also recommended continuation of antiobesity in the US and around the world. Pharmacotherapy
medications during weight loss maintenance, and has historically been viewed by many physicians as a
suggested a more detailed plan for antiobesity fringe treatment, resulting in the persistence of “eat
medication monitoring.11 The Endocrine Society less, move more” advice that fails to produce durable
advised against off-label prescribing of drug weight loss for most patients. This perception
treatments indicated for other purposes solely to has been reflected in the underuse of antiobesity
achieve weight loss. Lastly, this guideline allowed medications by a minority of clinicians. However,
for off-label, long term (>3 months) prescribing of the advent of newer, highly effective antiobesity
phentermine, for patients deemed safe candidates. medications has brought pharmacotherapy of obesity
In 2016, the American Association of Clinical into the mainstream, and patients are increasingly
Endocrinologists and the American College of asking their physicians for advice on these drug
Endocrinology also issued clinical practice guidelines treatments. Prescription rates are increasing rapidly,
for obesity.153 Although largely aligned with earlier leading to challenges in maintaining drug treatment
documents, these guidelines explicitly recommended supply.183 New antiobesity medications are on the
against the short term use of antiobesity medications horizon and will provide levels of efficacy that were

BMI ≥30 or 27-29.9 with weight related complication
• Patient has previous attempt at lifestyle based therapy with non-response or weight regain or
• As part of initial treatment if ≥10% weight loss clinically indicated
Initiate AOM* and lifestyle based therapy

Intolerance or adverse event Monthly check for 3 months†
• Discontinue and try another AOM* • Monitor for adverse events or intolerance
• Monitor weight loss
• Increase dose as needed per package insert
Is there ≥3-5% weight loss at 3 months†?

Maintain on tolerated and effective dose Inadequate response despite
• Monitor for adverse events or intolerance maximum tolerated dose
• Quarterly visits • Discontinue and try another AOM* or
• Modify lifestyle based therapy as needed • Add second agent with different
mechanism of action‡
Fig 1 | A guideline informed strategy for antiobesity medication prescribing. AOM=antiobesity medication. *After factoring in patient comorbidities,
preferences, and affordability/insurance coverage, clinicians could consider prioritizing based on expected weight loss, such as: - GLP-1 receptor
agonist (semaglutide/liraglutide (semaglutide produces more weight loss on average than liraglutide)) or dual agonist (tirzepatide) - Phentermine-
topiramate extended release - Bupropion-naltrexone sustained release - Phentermine monotherapy or similar (if patient is an appropriate candidate
and in concordance with regulations and guidelines in your institution or location) - Orlistat (if patient is unable to take other, more effective
drugs) †Depending on tolerability, some drug treatments can take longer than three months to reach full dosing. In these cases, longer monitoring
for weight loss and adverse events is indicated. ‡Current guidelines do not specifically advise this additive approach to pharmacotherapy; however,
the approach could be reasonable with individual patients under the care of an obesity medicine specialist (provided that the second agent is well
tolerated, affordable, sustainable and appears to benefit the patient). Further research is needed in this area to guide general practice
previously only seen with bariatric surgery. The hope benefits and drawbacks of antiobesity medications.
is that competition will bring down the cost of these Major research gaps remain around examining the
drug treatments over time, and insurance companies optimal clinical definition of obesity that warrants
will gradually provide coverage for antiobesity antiobesity medication treatment, the comparative
medications much as they do for new drug treatments effectiveness of antiobesity medication for outcomes
for other chronic metabolic diseases such as diabetes beyond weight loss, the utility of combination
and hyperlipidemia. Clinicians should work to therapy, determining how to personalize treatment
become comfortable having comprehensive yet for individual patients, and showing the cost
efficient conversations with their patients about the effectiveness of antiobesity medications.
KEY QUESTIONS FOR FUTURE RESEARCH ABOUT ANTIOBESITY MEDICATIONS

Outcomes beyond weight loss:
• Do antiobesity medications contribute to improved health outcomes beyond weight loss, such as reducing cardiovascular events or mortality?
• Can antiobesity medications affect other weight related health conditions, such as non-alcoholic fatty liver disease and cancer?
Predicting response to antiobesity medications:
• Can individual patient responses to various antiobesity medications be accurately predicted?
• Do specific subpopulations that respond better to certain antiobesity medications?
Balancing effectiveness and cost:
• What is the optimal approach to balance the effectiveness of newer, more expensive antiobesity medications with their high cost of treatment?
• Should older, less expensive antiobesity medications be considered for certain patient groups, and if so, which criteria should guide this selection?
Combination therapy:
• Is it beneficial to combine different antiobesity medications to achieve greater weight loss or maintain long term results?
• How should patients best be transitioned to combination therapy when a patient plateaus on a single antiobesity medication?
Comparison against metabolic/bariatric surgery:
• Are newer antiobesity medications more effective and/or safer than metabolic/bariatric surgery for treating patients with severe obesity?
Weight loss maintenance:
• How can weight loss be effectively maintained in the long term with antiobesity medications?
• Is there a role for more affordable antiobesity medications, cycling on/off approaches, or lower dose antiobesity medications in weight loss
maintenance?
Redefining success:
• Should the definition of success with antiobesity medications be individualized, considering factors like weight stability, improved HbA1c, or
appetite control?
• How can success criteria be adapted to better meet the unique needs of different patient populations?

pharmacological interventions for adults with obesity.
HOW PATIENTS WERE INVOLVED IN THE CREATION Gastroenterology 2022;163:1198-225. doi:10.1053/j.
OF THIS ARTICLE gastro.2022.08.045
11 Apovian CM, Aronne LJ, Bessesen DH, et al, Endocrine Society.
To inform the development of a manuscript that Pharmacological management of obesity: an endocrine Society
clinical practice guideline. J Clin Endocrinol Metab 2015;100:342-
helps clinicians better deal with patients’ needs and 62. doi:10.1210/jc.2014-3415
questions about antiobesity medication use, we 12 Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with
consulted patient experts representing individuals overweight and obesity: a systematic review and network meta-
analysis of randomised controlled trials. Lancet 2022;399:259-69.
with the lived experience of obesity. The Obesity Action doi:10.1016/S0140-6736(21)01640-8
Coalition (OAC), a patient advocacy organization based 13 Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and
in the United States, was contacted by the authors severe obesity among adults: United States, 2017-2018. NCHS Data
Brief 2020;360:1-8.
with a request for help in identifying people living 14 Afshin A, Forouzanfar MH, Reitsma MB, et al, GBD 2015 Obesity
with obesity who might be willing to provide input for Collaborators. Health effects of overweight and obesity in
195 countries over 25 years. N Engl J Med 2017;377:13-27.
this review. The four people listed in the contribution doi:10.1056/NEJMoa1614362
section were identified with the help of the OAC, 15 Chew NWS, Ng CH, Tan DJH, et al. The global burden of metabolic
and they reviewed a draft manuscript and provided disease: Data from 2000 to 2019. Cell Metab 2023;35:414-428.e3.
doi:10.1016/j.cmet.2023.02.003
input. These people emphasized the importance of 16 US Government Accountability Office. Obesity drugs: few adults used
recognizing obesity as a chronic disease, the profound prescription drugs for weight loss and insurance coverage varied.
impact that stigma and bias play in the ability of people 2019. https://www.gao.gov/products/gao-19-577
17 Samaranayake NR, Ong KL, Leung RY, Cheung BM. Management
living with obesity to get treatment, and the need of obesity in the National Health and Nutrition Examination
for access to antiobesity medications by improving Survey (NHANES), 2007-2008. Ann Epidemiol 2012;22:349-53.
provider comfort with prescribing and insurance doi:10.1016/j.annepidem.2012.01.001
18 Xia Y, Kelton CM, Guo JJ, Bian B, Heaton PC. Treatment of obesity:
coverage. Pharmacotherapy trends in the United States from 1999 to
2010. Obesity (Silver Spring) 2015;23:1721-8. doi:10.1002/
oby.21136
19 Del Re AC, Frayne SM, Harris AH. Antiobesity medication use across
We thank Patty Nece, Ian Patton, Maya Cohen, and Michele Tedder for the veterans health administration: patient-level predictors of receipt.
their thoughtful input and helpful comments during the development Obesity (Silver Spring) 2014;22:1968-72. doi:10.1002/oby.20810
of this review. 20 Saxon DR, Iwamoto SJ, Mettenbrink CJ, et al. Antiobesity medication
use in 2.2 million adults across eight large health care organizations:
Contributorship: All authors participated in the literature review, 2009-2015. Obesity (Silver Spring) 2019;27:1975-81.
interpretation of literature, drafting of the manuscript, and revision of doi:10.1002/oby.22581
the manuscript. DA is the guarantor. 21 Thomas CE, Mauer EA, Shukla AP, Rathi S, Aronne LJ. Low adoption
Competing interests: KHL reported receiving personal fees from of weight loss medications: A comparison of prescribing patterns
National Committee for Quality Assurance for serving as a faculty of antiobesity pharmacotherapies and SGLT2s. Obesity (Silver
member on a continuing medical education activity about obesity Spring) 2016;24:1955-61. doi:10.1002/oby.21533
outside the submitted work. 22 Claridy MD, Czepiel KS, Bajaj SS, Stanford FC. Treatment of obesity:
pharmacotherapy trends of office-based visits in the United
DA reported receiving reimbursement from the American Society States From 2011 to 2016. Mayo Clin Proc 2021;96:2991-3000.
for Metabolic and Bariatric Surgery for travel expenses to the 2023 doi:10.1016/j.mayocp.2021.07.021
annual meeting. 23 Thomas DD, Waring ME, Ameli O, Reisman JI, Vimalananda VG.
DHB has received research funding and compensation for consulting Patient characteristics associated with receipt of prescription
work from Eli Lilly and Novo Nordisk. weight-management medications among veterans participating in
MOVE!Obesity (Silver Spring) 2019;27:1168-76. doi:10.1002/
CES has no conflicts of interest to declare. oby.22503
Provenance and peer review: commissioned; externally peer 24 Levin A, Kaur N, Mainoo NK, Perez A. prevalence of antiobesity
reviewed. treatment and weight-inducing antihyperglycemic agents
among patients with type 2 diabetes in the United States. Clin
1 Frattini F, Lavazza M, Rausei S, Rovera F, Boni L, Dionigi G. BMI: the Ther 2022;44:e35-44. doi:10.1016/j.clinthera.2022.01.003
weakness of a milestone in obesity management and treatment. 25 Squadrito F, Rottura M, Irrera N, et al. Anti-obesity drug therapy
Obes Surg 2015;25:1940-1. doi:10.1007/s11695-015-1795-3 in clinical practice: Evidence of a poor prescriptive attitude.
2 Pajecki D, Dantas ACB, Santo MA, Tess BH. Beyond the BMI: a critical Biomed Pharmacother 2020;128:110320. doi:10.1016/j.
analysis of the Edmonton Obesity Staging System and the new biopha.2020.110320
guidelines for indications for metabolic and bariatric surgery. Obes 26 Elangovan A, Shah R, Smith ZL. pharmacotherapy for obesity-
Surg 2023;33:1276-8. doi:10.1007/s11695-023-06516-3 trends using a population level national database. Obes
3 Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause Surg 2021;31:1105-12. doi:10.1007/s11695-020-04987-2
mortality with overweight and obesity using standard body 27 Osterland A, King C, Kumar N, et al. Retrospective descriptive
mass index categories: a systematic review and meta-analysis. analysis of a managed care population with obesity. Curr Med Res
JAMA 2013;309:71-82. doi:10.1001/jama.2012.113905 Opin 2022;38:83-9. doi:10.1080/03007995.2021.1991900
4 Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to 28 Wright DR, Guo J, Hernandez I. A prescription for
insulin resistance and type 2 diabetes. Nature 2006;444:840-6. achieving equitable access to antiobesity medications.
doi:10.1038/nature05482 JAMA Health Forum 2023;4:e230493. doi:10.1001/
5 Cohen JB. Hypertension in obesity and the impact of weight loss. Curr jamahealthforum.2023.0493
Cardiol Rep 2017;19:98. doi:10.1007/s11886-017-0912-4 29 Kim HO, Lee JA, Suh HW, et al. Postmarketing surveillance study of the
6 Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep efficacy and safety of phentermine in patients with obesity. Korean J
apnea: a cardiometabolic risk in obesity and the metabolic syndrome. Fam Med 2013;34:298-306. doi:10.4082/kjfm.2013.34.5.298
J Am Coll Cardiol 2013;62:569-76. doi:10.1016/j.jacc.2013.05.045 30 Rocha-González HI, De la Cruz-Álvarez LE, Kammar-García A, et al.
7 Vina ER, Kwoh CK. Epidemiology of osteoarthritis: literature Weight loss at first month and development of tolerance as possible
update. Curr Opin Rheumatol 2018;30:160-7. doi:10.1097/ predictors of 30 mg phentermine efficacy at 6 months. J Pers
BOR.0000000000000479 Med 2021;11:1354. doi:10.3390/jpm11121354
8 Jastreboff AM, Kotz CM, Kahan S, Kelly AS, Heymsfield SB. Obesity 31 Moldovan CP, Weldon AJ, Daher NS, et al. Effects of a
as a disease: The Obesity Society 2018 position statement. Obesity meal replacement system alone or in combination with
(Silver Spring) 2019;27:7-9. doi:10.1002/oby.22378 phentermine on weight loss and food cravings. Obesity (Silver
9 Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, Spring) 2016;24:2344-50. doi:10.1002/oby.21649
and management of obesity. N Engl J Med 2017;376:254-66. 32 Acosta A, Camilleri M, Abu Dayyeh B, et al. Selection of antiobesity
doi:10.1056/NEJMra1514009 medications based on phenotypes enhances weight loss: a pragmatic
10 Grunvald E, Shah R, Hernaez R, et al, AGA Clinical trial in an obesity clinic. Obesity (Silver Spring) 2021;29:662-71.
Guidelines Committee. AGA clinical practice guideline on doi:10.1002/oby.23120

33 Lewis KH, Fischer H, Ard J, et al. Safety and effectiveness of 54 Apolzan JW, Venditti EM, Edelstein SL, et al, Diabetes Prevention
longer-term phentermine use: clinical outcomes from an electronic Program Research Group. Long-term weight loss with metformin
health record cohort. Obesity (Silver Spring) 2019;27:591-602. or lifestyle intervention in the Diabetes Prevention Program
doi:10.1002/oby.22430 Outcomes Study. Ann Intern Med 2019;170:682-90. doi:10.7326/
34 Grabarczyk TR. Observational comparative effectiveness of M18-1605
pharmaceutical treatments for obesity within the veterans health 55 Hudson JI, McElroy SL, Ferreira-Cornwell MC, Radewonuk J,
administration. Pharmacotherapy 2018;38:19-28. doi:10.1002/ Gasior M. Efficacy of lisdexamfetamine in adults with
phar.2048 moderate to severe binge-eating disorder: a randomized
35 Pérez-Cruz E, Guevara-Cruz M, Ortiz-Gutiérrez S, et al. Effect of clinical trial. JAMA Psychiatry 2017;74:903-10. doi:10.1001/
phentermine on hepatic steatosis in bariatric surgery: a pilot study. jamapsychiatry.2017.1889
Med Princ Pract 2022;31:254-61. doi:10.1159/000524805 56 Petrin C, Kahan S, Turner M, Gallagher C, Dietz WH. Current practices
36 Griebeler ML, Butsch WS, Rodriguez P, et al. The use of virtual of obesity pharmacotherapy, bariatric surgery referral and coding for
visits for obesity pharmacotherapy in patients with overweight counselling by healthcare professionals. Obes Sci Pract 2016;2:266-
or obesity compared with in-person encounters. Obesity (Silver 71. doi:10.1002/osp4.53
Spring) 2022;30:2194-203. doi:10.1002/oby.23548 57 Simon R, Lahiri SW. Provider practice habits and barriers to care in
37 Márquez-Cruz M, Kammar-García A, Huerta-Cruz JC, et al. Three- and obesity management in a large multicenter health system. Endocr
six-month efficacy and safety of phentermine in a Mexican obese Pract 2018;24:321-8. doi:10.4158/EP-2017-0221
population. Int J Clin Pharmacol Ther 2021;59:539-48. doi:10.5414/ 58 Gadde KM, Atkins KD. The limits and challenges of antiobesity
CP203943 pharmacotherapy. Expert Opin Pharmacother 2020;21:1319-28. doi:
38 Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight 10.1080/14656566.2020.1748599
loss and metabolic benefits with controlled-release phentermine/ 59 Granara B, Laurent J. Provider attitudes and practice patterns of
topiramate in obese and overweight adults (SEQUEL): a obesity management with pharmacotherapy. J Am Assoc Nurse
randomized, placebo-controlled, phase 3 extension study. Am J Clin Pract 2017;29:543-50. doi:10.1002/2327-6924.12481
Nutr 2012;95:297-308. doi:10.3945/ajcn.111.024927 60 Gudzune KA, Beach MC, Roter DL, Cooper LA. Physicians build less
39 Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, rapport with obese patients. Obesity (Silver Spring) 2013;21:2146-
controlled-release, phentermine plus topiramate combination on 52. doi:10.1002/oby.20384
weight and associated comorbidities in overweight and obese 61 Huizinga MM, Bleich SN, Beach MC, Clark JM, Cooper LA. Disparity
adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. in physician perception of patients’ adherence to medications
Lancet 2011;377:1341-52. doi:10.1016/S0140-6736(11)60205- by obesity status. Obesity (Silver Spring) 2010;18:1932-7.
5 doi:10.1038/oby.2010.35
40 Pi-Sunyer X, Astrup A, Fujioka K, et al, SCALE Obesity and Prediabetes 62 Puhl RM, Heuer CA. The stigma of obesity: a review and update.
NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg Obesity (Silver Spring) 2009;17:941-64. doi:10.1038/
of liraglutide in weight management. N Engl J Med 2015;373:11-22. oby.2008.636
doi:10.1056/NEJMoa1411892 63 Pachankis JE, Hatzenbuehler ML, Wang K, et al. The burden of
41 Clément K, van den Akker E, Argente J, et al, Setmelanotide POMC and stigma on health and well-being: a taxonomy of concealment,
LEPR Phase 3 Trial Investigators. Efficacy and safety of setmelanotide, course, disruptiveness, aesthetics, origin, and peril across
an MC4R agonist, in individuals with severe obesity due to LEPR or 93 stigmas. Pers Soc Psychol Bull 2018;44:451-74.
POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. doi:10.1177/0146167217741313
Lancet Diabetes Endocrinol 2020;8:960-70. doi:10.1016/S2213- 64 Phelan SM, Burgess DJ, Yeazel MW, Hellerstedt WL, Griffin JM, van
8587(20)30364-8 Ryn M. Impact of weight bias and stigma on quality of care and
42 Wilding JPH, Batterham RL, Calanna S, et al, STEP 1 Study Group. outcomes for patients with obesity. Obes Rev 2015;16:319-26.
Once-weekly semaglutide in adults with overweight or obesity. N Engl doi:10.1111/obr.12266
J Med 2021;384:989-1002. doi:10.1056/NEJMoa2032183 65 Tomiyama AJ, Finch LE, Belsky AC, et al. Weight bias in 2001 versus
43 Jastreboff AM, Aronne LJ, Ahmad NN, et al, SURMOUNT-1 2013: contradictory attitudes among obesity researchers and health
Investigators. Tirzepatide once weekly for the treatment of obesity. N professionals. Obesity (Silver Spring) 2015;23:46-53. doi:10.1002/
Engl J Med 2022;387:205-16. doi:10.1056/NEJMoa2206038 oby.20910
44 Astrup A, Caterson I, Zelissen P, et al. Topiramate: long-term 66 Wilson ER, Kyle TK, Nadglowski JFJr, Stanford FC. Obesity coverage
maintenance of weight loss induced by a low-calorie diet in gap: Consumers perceive low coverage for obesity treatments even
obese subjects. Obes Res 2004;12:1658-69. doi:10.1038/ when workplace wellness programs target BMI. Obesity (Silver
oby.2004.206 Spring) 2017;25:370-7. doi:10.1002/oby.21746
45 Eliasson B, Gudbjörnsdottir S, Cederholm J, Liang Y, Vercruysse F, 67 Gomez G, Stanford FC. US health policy and prescription drug
Smith U. Weight loss and metabolic effects of topiramate in coverage of FDA-approved medications for the treatment of
overweight and obese type 2 diabetic patients: randomized double- obesity. Int J Obes (Lond) 2018;42:495-500. doi:10.1038/
blind placebo-controlled trial. Int J Obes (Lond) 2007;31:1140-7. ijo.2017.287
doi:10.1038/sj.ijo.0803548 68 Jannah N, Hild J, Gallagher C, Dietz W. Coverage for obesity prevention
46 Rosenstock J, Hollander P, Gadde KM, Sun X, Strauss R, Leung A, OBD- and treatment services: analysis of medicaid and state employee
202 Study Group. A randomized, double-blind, placebo-controlled, health insurance programs. Obesity (Silver Spring) 2018;26:1834-
multicenter study to assess the efficacy and safety of topiramate 40. doi:10.1002/oby.22307
controlled release in the treatment of obese type 2 diabetic patients. 69 Baig K, Dusetzina SB, Kim DD, Leech AA. Medicare Part D coverage of
Diabetes Care 2007;30:1480-6. doi:10.2337/dc06-2001 antiobesity medications — challenges and uncertainty ahead. N Engl
47 Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, J Med 2023;388:961-3. doi:10.1056/NEJMp2300516
O’Neil PM. Bupropion SR enhances weight loss: a 48-week 70 Goodrx. Ozempic. Updated 2023. https://www.goodrx.com/ozempic
double-blind, placebo- controlled trial. Obes Res 2002;10:633-41. 71 Goodrx. Victoza. Updated 2023. https://www.goodrx.com/victoza
doi:10.1038/oby.2002.86 72 USC Schaeffer Center. Medicare coverage of weight loss drugs could
48 Booth K, Clements JN. Role of bupropion plus naltrexone for the significantly reduce costs. 2023. https://healthpolicy.usc.edu/article/
management of obesity. J Pharm Technol 2016;32:125-32. medicare-coverage-of-weight-loss-drugs-could-significantly-reduce-
doi:10.1177/8755122515624220 costs/
49 Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo- 73 World Health Organization. Shortages impacting access to glucagon-
controlled, dose-ranging trial of topiramate for weight loss in obesity. like peptide 1 receptor agonist products; increasing the potential
Obes Res 2003;11:722-33. doi:10.1038/oby.2003.102 for falsified versions. 2024. https://www.who.int/news/item/29-
50 Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M, OBES-002 01-2024-shortages-impacting-access-to-glucagon-like-peptide-1-
Study Group. A randomized double-blind placebo-controlled study receptor-agonist-products--increasing-the-potential-for-falsified-
of the long-term efficacy and safety of topiramate in the treatment of versions
obese subjects. Int J Obes Relat Metab Disord 2004;28:1399-410. 74 Bray GA. Medical treatment of obesity: the past, the present and
doi:10.1038/sj.ijo.0802783 the future. Best Pract Res Clin Gastroenterol 2014;28:665-84.
51 Jain AK, Kaplan RA, Gadde KM, et al. Bupropion SR vs. placebo for doi:10.1016/j.bpg.2014.07.015
weight loss in obese patients with depressive symptoms. Obes 75 Ahmad NN, Robinson S, Kennedy-Martin T, Poon JL, Kan H. Clinical
Res 2002;10:1049-56. doi:10.1038/oby.2002.142 outcomes associated with anti-obesity medications in real-world
52 Gadde KM, Xiong GL. Bupropion for weight reduction. Expert Rev practice: A systematic literature review. Obes Rev 2021;22:e13326.
Neurother 2007;7:17-24. doi:10.1586/14737175.7.1.17 doi:10.1111/obr.13326
53 McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety 76 Alsuhibani A, Alrasheed M, Gari M, Hincapie AL, Guo JJ. Descriptive
of lisdexamfetamine for treatment of adults with moderate analysis of reported adverse events associated with anti-obesity
to severe binge-eating disorder: a randomized clinical medications using FDA Adverse Event Reporting System (FAERS)
trial. JAMA Psychiatry 2015;72:235-46. doi:10.1001/ databases 2013-2020. Int J Clin Pharm 2022;44:172-9.
jamapsychiatry.2014.2162 doi:10.1007/s11096-021-01330-2

77 Turner M, Jannah N, Kahan S, Gallagher C, Dietz W. Current knowledge 98 Hansen KB, Svendstrup M, Lund A, Knop FK, Vilsbøll T, Vestergaard H.
of obesity treatment guidelines by health care professionals. Obesity Once-weekly subcutaneous semaglutide treatment for persons with
(Silver Spring) 2018;26:665-71. doi:10.1002/oby.22142 type 2 diabetes: real-world data from a diabetes out-patient clinic.
78 Iwamoto S, Saxon D, Tsai A, et al. Effects of education and experience Diabet Med 2021;38:e14655. doi:10.1111/dme.14655.
on primary care providers’ perspectives of obesity treatments 99 Holmes P, Bell HE, Bozkurt K, et al. Real-world use of once-weekly
during a pragmatic trial. Obesity (Silver Spring) 2018;26:1532-8. semaglutide in type 2 diabetes: results from the SURE UK multicentre,
doi:10.1002/oby.22223 prospective, observational study. Diabetes Ther 2021;12:2891-905.
79 Deng Y, Park A, Zhu L, Xie W, Pan CQ. Effect of doi:10.1007/s13300-021-01141-8
semaglutide and liraglutide in individuals with obesity 100 Marzullo P, Daffara T, Mele C, et al. Real-world evaluation of
or overweight without diabetes: a systematic review. weekly subcutaneous treatment with semaglutide in a cohort of
Ther Adv Chronic Dis 2022;13:20406223221108064. Italian diabetic patients. J Endocrinol Invest 2022;45:1587-98.
doi:10.1177/20406223221108064 doi:10.1007/s40618-022-01799-2
80 Leventhal-Perek S, Shani M, Schonmann Y. Effectiveness and 101 Menzen M, Berentzen TL, Catarig AM, Pieperhoff S, Simon J,
persistence of anti-obesity medications (liraglutide 3 mg, Jacob S. Real-world use of once-weekly semaglutide in type 2
lorcaserin, and orlistat) in a real-world primary care setting. Fam diabetes: results from SemaglUtide Real-world Evidence (SURE)
Pract 2023;40:629-37. doi:10.1093/fampra/cmac141 Germany. Exp Clin Endocrinol Diabetes 2023;131:205-15.
81 Ard JD, Beavers DP, Hale E, Miller G, McNatt S, Fernandez A. Use doi:10.1055/a-2007-2061
of phentermine-topiramate extended release in combination 102 Pérez-Belmonte LM, Sanz-Cánovas J, García de Lucas MD, et al.
with sleeve gastrectomy in patients with BMI 50 kg/m2 or Efficacy and safety of semaglutide for the management of obese
more. Surg Obes Relat Dis 2019;15:1039-43. doi:10.1016/j. patients with type 2 diabetes and chronic heart failure in real-world
soard.2019.04.017 clinical practice. Front Endocrinol (Lausanne) 2022;13:851035.
82 Muratori F, Vignati F, Di Sacco G, Gavazzi L, Pellegrino D, Del doi:10.3389/fendo.2022.851035
Prete M. Efficacy of liraglutide 3.0 mg treatment on weight loss 103 Rajamand Ekberg N, Bodholdt U, Catarig AM, et al. Real-world
in patients with weight regain after bariatric surgery. Eat Weight use of once-weekly semaglutide in patients with type 2 diabetes:
Disord 2022;27:2775-81. doi:10.1007/s40519-022-01403-9 Results from the SURE Denmark/Sweden multicentre, prospective,
83 Pantalone KM, Smolarz BG, Ramasamy A, et al. Effectiveness of observational study. Prim Care Diabetes 2021;15:871-8.
combining antiobesity medication with an employer-based weight doi:10.1016/j.pcd.2021.06.008
management program for treatment of obesity: a randomized 104 Rudofsky G, Catarig AM, Favre L, et al. Real-world use of once-
clinical trial. JAMA Netw Open 2021;4:e2116595. doi:10.1001/ weekly semaglutide in patients with type 2 diabetes: Results from
jamanetworkopen.2021.16595 the SURE Switzerland multicentre, prospective, observational
84 Calderon G, Gonzalez-Izundegui D, Shan KL, et al. Effectiveness study. Diabetes Res Clin Pract 2021;178:108931. doi:10.1016/j.
of anti-obesity medications approved for long-term use in a diabres.2021.108931
multidisciplinary weight management program: a multi-center clinical 105 White GE, Shu I, Rometo D, Arnold J, Korytkowski M, Luo J. Real-world
experience. Int J Obes (Lond) 2022;46:555-63. doi:10.1038/ weight-loss effectiveness of glucagon-like peptide-1 agonists among
s41366-021-01019-6 patients with type 2 diabetes: A retrospective cohort study. Obesity
85 Trenson L, Trenson S, van Nes F, et al. Liraglutide for weight (Silver Spring) 2023;31:537-44. doi:10.1002/oby.23622
management in the real world: significant weight loss even if the 106 Williams DM, Ruslan AM, Khan R, et al. Real-world clinical experience
maximal daily dose is not achieved. Obes Facts 2022;15:83-9. of semaglutide in secondary care diabetes: a retrospective
doi:10.1159/000520217 observational study. Diabetes Ther 2021;12:801-11. doi:10.1007/
86 Haase CL, Serratore Achenbach MG, Lucrezi G, Jeswani N, Maurer S, s13300-021-01015-z
Egermann U. Use of liraglutide 3.0 mg for weight management in 107 Wolffenbuttel BHR, Brugts MP, Catarig AM, et al. Once-weekly
a real-world setting in Switzerland. Obes Facts 2021;14:568-76. semaglutide use in type 2 diabetes: real-world Data from the SURE
doi:10.1159/000518325 Netherlands observational study. Adv Ther 2023;40:920-33.
87 Park JH, Kim JY, Choi JH, et al. Effectiveness of liraglutide 3 mg for the doi:10.1007/s12325-022-02385-x
treatment of obesity in a real-world setting without intensive lifestyle 108 Jain AB, Kanters S, Khurana R, Kissock J, Severin N, Stafford SG.
intervention. Int J Obes (Lond) 2021;45:776-86. doi:10.1038/ Real-world effectiveness analysis of switching from liraglutide or
s41366-021-00739-z dulaglutide to semaglutide in patients with type 2 diabetes mellitus:
88 Park JS, Kwon J, Choi HJ, Lee C. Clinical effectiveness of liraglutide the retrospective REALISE-DM study. Diabetes Ther 2021;12:527-36.
on weight loss in South Koreans: First real-world retrospective data doi:10.1007/s13300-020-00984-x
on Saxenda in Asia. Medicine (Baltimore) 2021;100:e23780. 109 Nor Hanipah Z, Nasr EC, Bucak E, et al. Efficacy of adjuvant
doi:10.1097/MD.0000000000023780 weight loss medication after bariatric surgery. Surg Obes Relat
89 Wharton S, Haase CL, Kamran E, et al. Weight loss and persistence Dis 2018;14:93-8. doi:10.1016/j.soard.2017.10.002
with liraglutide 3.0 mg by obesity class in the real-world effectiveness 110 Hendricks EJ, Rothman RB, Greenway FL. How physician
study in Canada. Obes Sci Pract 2020;6:439-44. doi:10.1002/ obesity specialists use drugs to treat obesity. Obesity (Silver
osp4.420 Spring) 2009;17:1730-5. doi:10.1038/oby.2009.69
90 Wharton S, Kuk JL, Luszczynski M, Kamran E, Christensen RAG. 111 Costello T, Dorrell M, Kellams T, Kraska K. Review of pharmacologic
Liraglutide 3.0 mg for the management of insufficient weight weight loss medications in a patient-centered medical home. J Pharm
loss or excessive weight regain post-bariatric surgery. Clin Technol 2016;32:37-41. doi:10.1177/8755122515604858
Obes 2019;9:e12323. doi:10.1111/cob.12323 112 Shibuya K, Ali KF, Ji X, et al. The benefit of short-term weight loss
91 Wharton S, Liu A, Pakseresht A, et al. Real-world clinical effectiveness with anti-obesity medications in real-world clinical Practice. Endocr
of liraglutide 3.0 mg for weight management in Canada. Obesity Pract 2019;25:1022-8. doi:10.4158/EP-2019-0081
(Silver Spring) 2019;27:917-24. doi:10.1002/oby.22462 113 Elhag W, El Ansari W, Abdulrazzaq S, Elsherif M, Mustafa I. Lorcaserin
92 Santini S, Vionnet N, Pasquier J, et al. Marked weight loss on vs. Phentermine among non-surgical and surgical obese patients:
liraglutide 3.0 mg: Real-life experience of a Swiss cohort with obesity. Anthropometric, glycemic, lipid, safety and cost outcomes. Ann Med
Obesity (Silver Spring) 2023;31:74-82. doi:10.1002/oby.23596 Surg (Lond) 2019;45:75-81. doi:10.1016/j.amsu.2019.07.024
93 Tchang BG, Aras M, Wu A, Aronne LJ, Shukla AP. Long-term weight 114 Li Z, Hong K, Yip I, et al. Body weight loss with phentermine alone
loss maintenance with obesity pharmacotherapy: A retrospective versus phentermine and fenfluramine with very-low-calorie diet in
cohort study. Obes Sci Pract 2021;8:320-7. doi:10.1002/osp4.575 an outpatient obesity management program: a retrospective study.
94 Ghusn W, De la Rosa A, Sacoto D, et al. Weight loss outcomes Curr Ther Res Clin Exp 2003;64:447-60. doi:10.1016/S0011-
associated with semaglutide treatment for patients with overweight 393X(03)00126-7
or obesity. JAMA Netw Open 2022;5:e2231982. doi:10.1001/ 115 Schwartz J, Chaudhry UI, Suzo A, et al. Erratum to: Pharmacotherapy
jamanetworkopen.2022.31982 in conjunction with a diet and exercise program for the treatment
95 Berra CC, Rossi MC, Mirani M, et al. Real world effectiveness of weight recidivism or weight-loss plateau post-bariatric surgery:
of subcutaneous semaglutide in type 2 diabetes: A a retrospective review. Obes Surg 2016;26:706. doi:10.1007/
retrospective, cohort study (Sema-MiDiab01). Front Endocrinol s11695-015-2044-5
(Lausanne) 2023;13:1099451. doi:10.3389/fendo.2022.1099451 116 Toth AT, Gomez G, Shukla AP, et al. Weight loss medications in
96 Brown RE, Bech PG, Aronson R. Semaglutide once weekly young adults after bariatric surgery for weight regain or inadequate
in people with type 2 diabetes: Real-world analysis of the weight loss: a multi-center study. Children (Basel) 2018;5:116.
Canadian LMC diabetes registry (SPARE study). Diabetes Obes doi:10.3390/children5090116
Metab 2020;22:2013-20. doi:10.1111/dom.14117 117 Hollywood A, Ogden J. Taking orlistat: predicting weight loss over 6
97 Crabtree TSJ, Adamson K, Reid H, et al, all ABCD semaglutide audit months. J Obes 2011;2011:806896. doi:10.1155/2011/806896
contributors. Injectable semaglutide and reductions in HbA1c 118 Rowe R, Cowx M, Poole C, McEwan P, Morgan C, Walker M. The effects
and weight in the real world in people switched from alternative of orlistat in patients with diabetes: improvement in glycaemic
glucagon-like peptide-1 receptor agonists. Diabetes Obes control and weight loss. Curr Med Res Opin 2005;21:1885-90.
Metab 2022;24:1398-401. doi:10.1111/dom.14701 doi:10.1185/030079905X74943

119 Schwartz SM, Bansal VP, Hale C, Rossi M, Engle JP. Compliance, of obesity: An indirect treatment comparison. Diabetes Obes
behavior change, and weight loss with orlistat in an over-the-counter Metab 2023;25:2626-33. doi:10.1111/dom.15148
setting. Obesity (Silver Spring) 2008;16:623-9. doi:10.1038/ 141 Kim N, Wang J, Burudpakdee C, et al. Cost-effectiveness analysis
oby.2007.96 of semaglutide 2.4 mg for the treatment of adult patients with
120 Wirth A. Reduction of body weight and co-morbidities by orlistat: The overweight and obesity in the United States. J Manag Care Spec
XXL--Primary Health Care Trial. Diabetes Obes Metab 2005;7:21-7. Pharm 2022;28:740-52. doi:10.18553/jmcp.2022.28.7.740
doi:10.1111/j.1463-1326.2004.00428.x 142 Lee M, Lauren BN, Zhan T, et al. The cost-effectiveness of
121 Ahn SM, Kim H, Ji E, Han N, Oh JM. The effect of orlistat on weight pharmacotherapy and lifestyle intervention in the treatment of
reduction in obese and overweight Korean patients. Arch Pharm obesity. Obes Sci Pract 2019;6:162-70. doi:10.1002/osp4.390
Res 2014;37:512-9. doi:10.1007/s12272-013-0201-8 143 Atlas SJ, Beinfeld M, Lancaster V, et al. Medications for obesity
122 Allie EC, Kane MP, Busch RS, Bakst G, Hamilton RA. Orlistat in management: effectiveness and value. Institute for Clinical
obese patients with type 2 diabetes: a retrospective assessment and Economic Review. 2022. https://icer.org/wp-content/
of weight loss and metabolic effects. Hosp Pharm 2004;39:37-42. uploads/2022/03/ICER_Obesity_Evidence_Report_083122.pdf
doi:10.1177/001857870403900114 144 Bomberg EM, Ryder JR, Brundage RC, et al. Precision medicine
123 Beermann B, Melander H, Säwe J, Ulleryd C, Dahlqvist R. Incorrect use in adult and pediatric obesity: a clinical perspective. Ther
and limited weight reduction of orlistat (Xenical) in clinical practice. Adv Endocrinol Metab 2019;10:2042018819863022.
A cohort study. Eur J Clin Pharmacol 2001;57:309-11. doi:10.1007/ doi:10.1177/2042018819863022
s002280100316 145 Hinney A, Körner A, Fischer-Posovszky P. The promise of new anti-
124 Graham MR, Landgraf CG, Lindsey CC. A comparison of orlistat use obesity therapies arising from knowledge of genetic obesity traits.
in a veteran population: a pharmacist-managed pharmacotherapy Nat Rev Endocrinol 2022;18:623-37. doi:10.1038/s41574-022-
weight-loss clinic versus standard medical care. J Pharm 00716-0
Technol 2003;19:343-8. doi:10.1177/875512250301900601 146 Grilo CM, Lydecker JA, Fineberg SK, Moreno JO, Ivezaj V,
125 Douglas IJ, Bhaskaran K, Batterham RL, Smeeth L. The effectiveness Gueorguieva R. Naltrexone-bupropion and behavior therapy, alone
of pharmaceutical interventions for obesity: weight loss with orlistat and combined, for binge-eating disorder: randomized double-
and sibutramine in a United Kingdom population-based cohort. Br J blind placebo-controlled trial. Am J Psychiatry 2022;179:927-37.
Clin Pharmacol 2015;79:1020-7. doi:10.1111/bcp.12578 doi:10.1176/appi.ajp.20220267
126 Horie NC, Cercato C, Mancini MC, Halpern A. Long-term 147 Dalton M, Finlayson G, Walsh B, Halseth AE, Duarte C, Blundell JE.
pharmacotherapy for obesity in elderly patients: a retrospective Early improvement in food cravings are associated with long-
evaluation of medical records from a specialized obesity outpatient term weight loss success in a large clinical sample. Int J Obes
clinic. Drugs Aging 2010;27:497-506. doi:10.2165/11536660- (Lond) 2017;41:1232-6. doi:10.1038/ijo.2017.89
000000000-00000 148 Thomas EA, Mcnair B, Bechtell JL, Ferland A, Cornier MA, Eckel RH.
127 Gorgojo-Martínez JJ, Basagoiti-Carreño B, Sanz-Velasco A, Serrano- Greater hunger and less restraint predict weight loss success with
Moreno C, Almodóvar-Ruiz F. Effectiveness and tolerability of orlistat phentermine treatment. Obesity (Silver Spring) 2016;24:37-43.
and liraglutide in patients with obesity in a real-world setting: The doi:10.1002/oby.21244
XENSOR Study. Int J Clin Pract 2019;73:e13399. doi:10.1111/ 149 Srivastava G, Apovian C. Future pharmacotherapy for obesity: new
ijcp.13399 anti-obesity drugs on the horizon. Curr Obes Rep 2018;7:147-61.
128 Gillani S, Singh B. The use of GLP-1 agonist therapy, liraglutide, doi:10.1007/s13679-018-0300-4
is associated with significant weight loss in morbidly obese 150 Hollander P, Bays HE, Rosenstock J, et al. Coadministration of
people without diabetes. Br J Diabetes Vasc Dis 2015;15:61-4. canagliflozin and phentermine for weight management in overweight
doi:10.15277/bjdvd.2015.011 and obese individuals without diabetes: a randomized clinical trial.
129 Ferrari F, Fierabracci P, Salvetti G, et al. Weight loss effect of liraglutide Diabetes Care 2017;40:632-9. doi:10.2337/dc16-2427
in real-life: the experience of a single Italian obesity center. J 151 Ludvik B, Frías JP, Tinahones FJ, et al. Dulaglutide as add-on therapy
Endocrinol Invest 2020;43:1779-85. doi:10.1007/s40618-020- to SGLT2 inhibitors in patients with inadequately controlled type
01334-1 2 diabetes (AWARD-10): a 24-week, randomised, double-blind,
130 Chou CA, Chuang SF. Evaluation of the efficacy of low-dose liraglutide placebo-controlled trial. Lancet Diabetes Endocrinol 2018;6:370-81.
in weight control among Taiwanese non-diabetes patients. J Diabetes doi:10.1016/S2213-8587(18)30023-8
Investig 2020;11:1524-31. doi:10.1111/jdi.13314 152 Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability,
131 Sauer N, Reining F, Schulze Zur Wiesch C, Burkhardt T, Aberle J. Off- pharmacokinetics, and pharmacodynamics of concomitant
label antiobesity treatment in patients without diabetes with GLP-1 administration of multiple doses of cagrilintide with semaglutide
agonists in clinical practice. Horm Metab Res 2015;47:560-4. 2·4 mg for weight management: a randomised, controlled, phase
132 Suliman M, Buckley A, Al Tikriti A, et al. Routine clinical use 1b trial. Lancet 2021;397:1736-48. doi:10.1016/S0140-
of liraglutide 3 mg for the treatment of obesity: Outcomes in 6736(21)00845-X
non-surgical and bariatric surgery patients. Diabetes Obes 153 Garvey WT, Mechanick JI, Brett EM, et al, Reviewers of the AACE/
Metab 2019;21:1498-501. doi:10.1111/dom.13672 ACE Obesity Clinical Practice Guidelines. American Association of
133 Rye P, Modi R, Cawsey S, Sharma AM. Efficacy of high-dose liraglutide Clinical Endocrinologists and American College of Endocrinology
as an adjunct for weight loss in patients with prior bariatric surgery. comprehensive clinical practice guidelines for medical care of
Obes Surg 2018;28:3553-8. doi:10.1007/s11695-018-3393-7 patients with obesity. Endocr Pract 2016;22(Suppl 3):1-203.
134 Ganguly R, Tian Y, Kong SX, et al. Persistence of newer anti- doi:10.4158/EP161365.GL
obesity medications in a real-world setting. Diabetes Res Clin 154 ElSayed NA, Aleppo G, Aroda VR, et al, on behalf of the American
Pract 2018;143:348-56. doi:10.1016/j.diabres.2018.07.017 Diabetes Association. 9. Pharmacologic approaches to glycemic
135 Rubino DM, Greenway FL, Khalid U, et al, STEP 8 Investigators. treatment: standards of care in diabetes-2023. Diabetes
Effect of weekly subcutaneous semaglutide vs daily liraglutide on Care 2023;46(Suppl 1):S140-57. doi:10.2337/dc23-S009
body weight in adults with overweight or obesity without diabetes: 155 James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline
the STEP 8 randomized clinical trial. JAMA 2022;327:138-50. for the management of high blood pressure in adults: report from the
doi:10.1001/jama.2021.23619 panel members appointed to the Eighth Joint National Committee
136 Pratley R, Amod A, Hoff ST, et al, PIONEER 4 investigators. Oral (JNC 8). JAMA 2014;311:507-20. doi:10.1001/jama.2013.284427
semaglutide versus subcutaneous liraglutide and placebo in type 2 156 Rubino D, Abrahamsson N, Davies M, et al, STEP 4 Investigators.
diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Effect of continued weekly subcutaneous semaglutide vs placebo
Lancet 2019;394:39-50. doi:10.1016/S0140-6736(19)31271-1 on weight loss maintenance in adults with overweight or obesity:
137 Capehorn MS, Catarig AM, Furberg JK, et al. Efficacy and safety of the STEP 4 randomized clinical trial. JAMA 2021;325:1414-25.
once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as doi:10.1001/jama.2021.3224
add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes 157 Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin
(SUSTAIN 10). Diabetes Metab 2020;46:100-9. doi:10.1016/j. Nutr 2005;82(Suppl):222S-5S. doi:10.1093/ajcn/82.1.222S
diabet.2019.101117 158 Semaglutide: drug information. 2023. https://www.uptodate.com
138 O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of 159 Baig K, Dusetzina SB, Kim DD, Leech AA. Medicare Part D coverage of
semaglutide compared with liraglutide and placebo for weight loss antiobesity medications - challenges and uncertainty ahead. N Engl J
in patients with obesity: a randomised, double-blind, placebo and Med 2023;388:961-3. doi:10.1056/NEJMp2300516
active controlled, dose-ranging, phase 2 trial. Lancet 2018;392:637- 160 Lincoff AM, Brown-Frandsen K, Colhoun HM, et al, SELECT Trial
49. doi:10.1016/S0140-6736(18)31773-2 Investigators. Semaglutide and cardiovascular outcomes in obesity
139 Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. without diabetes. N Engl J Med 2023;389:2221-32. doi:10.1056/
Evaluation of phentermine and topiramate versus phentermine/ NEJMoa2307563
topiramate extended-release in obese adults. Obesity (Silver 161 Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al, STEP-HFpEF
Spring) 2013;21:2163-71. doi:10.1002/oby.20584 Trial Committees and Investigators. Semaglutide in patients with
140 le Roux CW, Hankosky ER, Wang D, et al. Tirzepatide 10 and heart failure with preserved ejection fraction and obesity. N Engl J
15 mg compared with semaglutide 2.4 mg for the treatment Med 2023;389:1069-84. doi:10.1056/NEJMoa2306963

162 Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, type 2 diabetes: a 54-week randomized phase 2b study. Diabetes
Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year Care 2021;44:1433-42. doi:10.2337/dc20-2151
type 2 diabetes risk in adults with overweight or obesity. Obesity 173 Jastreboff AM, Kaplan LM, Frías JP, et al, Retatrutide Phase 2 Obesity
(Silver Spring) 2023;31:2249-59. doi:10.1002/oby.23842 Trial Investigators. Triple–hormone-receptor agonist retatrutide
163 Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for obesity — a phase 2 trial. N Engl J Med 2023;389:514-26.
for type 2 diabetes and obesity. Peptides 2023;161:170939. doi:10.1056/NEJMoa2301972
doi:10.1016/j.peptides.2023.170939 174 Bossart M, Wagner M, Elvert R, et al. Effects on weight loss and
164 Knop FK, Aroda VR, do Vale RD, et al, OASIS 1 Investigators. Oral glycemic control with SAR441255, a potent unimolecular peptide
semaglutide 50 mg taken once per day in adults with overweight or GLP-1/GIP/GCG receptor triagonist. Cell Metab 2022;34:59-74.e10.
obesity (OASIS 1): a randomised, double-blind, placebo-controlled, doi:10.1016/j.cmet.2021.12.005
phase 3 trial. Lancet 2023;402:705-19. doi:10.1016/S0140- 175 Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of
6736(23)01185-6 co-administered once-weekly cagrilintide 2·4 mg with once-weekly
165 Wharton S, Blevins T, Connery L, et al, GZGI Investigators. Daily oral semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised,
GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J double-blind, active-controlled, phase 2 trial. Lancet 2023;402:720-
Med 2023;389:877-88. doi:10.1056/NEJMoa2302392 30. doi:10.1016/S0140-6736(23)01163-7
166 Saxena AR, Frias JP, Gorman DN, et al. Tolerability, safety and 176 Heymsfield SB, Coleman LA, Miller R, et al. Effect of
pharmacodynamics of oral, small-molecule glucagon-like peptide-1 bimagrumab vs placebo on body fat mass among adults with
receptor agonist danuglipron for type 2 diabetes: A 12-week, type 2 diabetes and obesity: a phase 2 randomized clinical
randomized, placebo-controlled, Phase 2 study comparing different trial. JAMA Netw Open 2021;4:e2033457. doi:10.1001/
dose-escalation schemes. Diabetes Obes Metab 2023;25:2805-14. jamanetworkopen.2020.33457
doi:10.1111/dom.15168 177 Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline
167 Jastreboff AM, Aronne LJ, Ahmad NN, et al, SURMOUNT-1 for the management of overweight and obesity in adults: a report of
Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. the American College of Cardiology/American Heart Association Task
N Engl J Med 2022;387:205-16. doi:10.1056/NEJMoa2206038 Force on Practice Guidelines and The Obesity Society. Circulation
168 Garvey WT, Frias JP, Jastreboff AM, et al, SURMOUNT-2 investigators. 2014;129:S102-38. 01.cir.0000437739.71477.ee
Tirzepatide once weekly for the treatment of obesity in people 178 Wharton S, Lau DCW, Vallis M, et al. Obesity in adults: a clinical
with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, practice guideline. CMAJ 2020;192:E875-91. doi:10.1503/
multicentre, placebo-controlled, phase 3 trial. Lancet 2023;402:613- cmaj.191707
26. doi:10.1016/S0140-6736(23)01200-X 179 Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and
169 Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after overweight. Cochrane Database Syst Rev 2004;2003:CD004094.
intensive lifestyle intervention in adults with overweight or obesity: 180 Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J.
the SURMOUNT-3 phase 3 trial. Nat Med 2023;29:2909-18. Pharmacotherapy for weight loss in adults with type 2 diabetes
doi:10.1038/s41591-023-02597-w mellitus. Cochrane Database Syst Rev 2005;2005:CD004096.
170 Ji L, Gao L, Jiang H, et al. Safety and efficacy of a GLP-1 and doi:10.1002/14651858.CD004096.pub2
glucagon receptor dual agonist mazdutide (IBI362) 9 mg 181 Siebenhofer A, Winterholer S, Jeitler K, et al. Long-term effects of
and 10 mg in Chinese adults with overweight or obesity: A weight-reducing drugs in people with hypertension. Cochrane
randomised, placebo-controlled, multiple-ascending-dose phase Database Syst Rev 2021;1:CD007654.
1b trial. EClinicalMedicine 2022;54:101691. doi:10.1016/j. 182 LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M,
eclinm.2022.101691 O’Connor EA. Behavioral and pharmacotherapy weight loss
171 Jungnik A, Arrubla Martinez J, Plum-Mörschel L, et al. Phase I studies interventions to prevent obesity-related morbidity and mortality
of the safety, tolerability, pharmacokinetics and pharmacodynamics in adults: updated evidence report and systematic review for the
of the dual glucagon receptor/glucagon-like peptide-1 receptor US Preventive Services Task Force. JAMA 2018;320:1172-91.
agonist BI 456906. Diabetes Obes Metab 2023;25:1011-23. doi:10.1001/jama.2018.7777
doi:10.1111/dom.14948 183 Sumithran P, Finucane FM, Cohen RV. Obesity drug shortages
172 Nahra R, Wang T, Gadde KM, et al. Effects of cotadutide on metabolic are symptomatic of wider malaise. Lancet 2023;S0140-
and hepatic parameters in adults with overweight or obesity and 6736(23)01963-3.

Effectiveness and Safety of Drugs For Obesity BJM 2022

Uploaded by

Document Informationclick to expand document information

Document Informationclick to expand document information

Copyright:

Available Formats

Effectiveness and Safety of Drugs For Obesity BJM 2022

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Effectiveness and Safety of Drugs For Obesity BJM 2022

Uploaded by

Copyright:

Available Formats

STATE OF THE ART REVIEW

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 1

Epidemiology naltrexone”, “semaglutide”, “liraglutide”,

2 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 3

4 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 5

6 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

and specialty clinics affiliated with an academic Semaglutide

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 7

8 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 9

10 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 11

Initiate AOM* and lifestyle based therapy

Is there ≥3-5% weight loss at 3 months†?

KEY QUESTIONS FOR FUTURE RESEARCH ABOUT ANTIOBESITY MEDICATIONS

12 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 13

14 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 15

16 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 17

You might also like

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 1

2 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 3

4 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 5

6 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 7

8 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 9

10 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 11

12 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 13

14 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 15

16 doi: 10.1136/bmj-2022-072686 | BMJ 2024;384:e072686 | the bmj

the bmj | BMJ 2024;384:e072686 | doi: 10.1136/bmj-2022-072686 17