Search Results (118)

Kidney disease is a public health epidemic affecting 10% of the population worldwide with a constantly rising incidence, and it is an important contributor to morbidity and mortality. Type 2 diabetes mellitus (T2DM) is a chronic complex condition with a rising incidence worldwide. T2DM remains the principal cause of chronic kidney disease (CKD), which is related to a high risk for cardiovascular (CV) events, end-stage kidney disease (ESKD), and, overall, considerable morbidity and mortality. In the past few decades, various therapeutic treatments have targeted the culprit pathways for slowing CKD progression, with partial success. Thus, despite new advances in patients’ treatment, progressive loss of kidney function or death from T2DM and CKD complications compel new therapeutic pathways. Renin–angiotensin–aldosterone-system-blocking agents have been the only treatment until recently. On top of this, sodium–glucose co-transporter 2 inhibitors along with finerenone showed an impressive ability to reduce the progression of kidney disease and cardiovascular events in diabetic patients with CKD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can play a special role and could be a game changer in this field. The latest FLOW trial confirmed multiple favorable clinical effects on renal, cardiovascular, and survival outcomes among high-risk patients treated with semaglutide and supports a significant therapeutic role for GLP-1RAs in this population, although larger-scale evaluation of their risks is needed, given their increasing use. Full article

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects. Full article

This study examines the in vitro effects of a soluble protein hydrolysate (SPH) derived from Atlantic salmon (Salmo salar) on incretin receptor activity and pancreatic islet cell protection to explore the mechanisms underlying SPH’s observed benefits on weight loss and metabolic health in overweight individuals. SPH demonstrated a dose-dependent enhancement of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor activity, with significant increases of 2.4-fold (p < 0.05) and 2.6-fold (p < 0.01) at 10 mg/mL, respectively, compared to the control. Pancreatic islet cell assays showed a substantial proliferation effect, with up to a 57% increase at 50 µL/well, indicating potential protective properties against inflammation-induced cell loss. Notably, the smallest SPH peptide fraction (<1000 Da) exhibited GLP-1 agonist activity comparable to semaglutide, a widely used therapeutic agent, underscoring SPH’s potential efficacy in modulating metabolic pathways. These results suggest that SPH not only enhances key incretin signaling but also promotes islet cell health, positioning it as a promising dietary intervention to improve age-related metabolic health, including the weight gain and underlying adverse metabolic changes frequently encountered through the menopause. Full article

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = −0.8%; p = 0.0053), weight (MD = −2.4 kg; p = 0.0253), and daily basal insulin dose (MD = −2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = −0.5%; p = 0.0004), weight (MD = −3.6 kg; p < 0.0001), and daily basal insulin (MD = −2.4 units; p = 0.0282) were significantly reduced at the 4–6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events. Full article

Diabetes medications can affect weight and cardiovascular health. Some medications can aid in weight management, while others may lead to weight gain. Patients must be monitored and receive appropriate care to manage weight and prevent cardiovascular complications. Despite advancements in diabetes treatments that can influence weight and cardiovascular outcomes, ongoing research is necessary in this intricate field. Long-term effects, individual variations, and combination therapies are still subjects of uncertainty and ongoing investigation. The major objective of the research is to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on body weight in diabetic patients through a scientometric assessment. Methodology: Research data were gathered from the Web of Science Core Collection (WoSCC) database by searching for the keywords “Body Weight”, dulaglutide, and semaglutide, identifying 60 relevant articles in the field. While there are advantages in managing diseases in which the cardiovascular system is implicated, there are also clinical considerations for personalized medicine and shared decision-making. The scientometric analysis of the articles revealed important insights into how dulaglutide and semaglutide impact weight management and their potential benefits for managing cardiovascular diseases in individuals with diabetes. Conclusions: Semaglutide shows superior outcomes compared to other commercially available GLP-1RAs, particularly in improving blood sugar control, lowering body weight, and addressing other cardio-metabolic risk factors in individuals with type 2 diabetes (T2DM). The findings suggest that GLP-1 RAs have the potential to provide cardiovascular protection by influencing various physiological factors such as blood pressure, pulse rate, glycated hemoglobin (HbA1c) levels, and the urinary albumin-to-creatinine ratio (RAC). The development and validation of the 4GI model provides a sophisticated tool for evaluating the complex interactions involved in diabetes treatments, offering insights into the mechanisms of action of various medications. Full article

Background: The increased popularity and ubiquitous use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of diabetes, heart failure, and obesity has led to significant concern for increased risk for perioperative aspiration, given their effects on delayed gastric emptying. This concern is highlighted by many major societies that have published varying guidance on the perioperative management of these medications, given limited data. We conducted a scoping review of the available literature regarding the aspiration risk and aspiration/regurgitant events related to GLP-1 RAs. Methods: A librarian-assisted search was performed using five electronic medical databases (PubMed, Embase, and Web of Science Platform Databases, including Web of Science Core Collection, KCI Korean Journal Database, MEDLINE, and Preprint Citation Index) from inception through March 2024 for articles that reported endoscopic, ultrasound, and nasogastric evaluation for increased residual gastric volume retained food contents, as well as incidences of regurgitation and aspiration events. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. Results: Of the 3712 citations identified, 24 studies met eligibility criteria. Studies included four prospective, six retrospective, five case series, and nine case reports. The GLP-1 RAs reported in the studies included semaglutide, liraglutide, lixisenatide, dulaglutide, tirzepatide, and exenatide. All studies, except one case report, reported patients with confounding factors for retained gastric contents and aspiration, such as a history of diabetes, cirrhosis, hypothyroidism, psychiatric disorders, gastric reflux, Barrett’s esophagus, Parkinson’s disease, dysphagia, obstructive sleep apnea, gastric polyps, prior abdominal surgeries, autoimmune diseases, pain, ASA physical status classification, procedural factors (i.e., thyroid surgery associated with risk for nausea, ketamine associated with nausea and secretions), and/or medications associated with delayed gastric emptying (opioids, anticholinergics, antidepressants, beta-blockers, calcium channel blockers, DPP-IV inhibitors, and antacids). Of the eight studies (three prospective and five retrospective) that evaluated residual contents in both GLP-1 users and non-users, seven studies (n = 7/8) reported a significant increase in residual gastric contents in GLP-1 users compared to non-users (19–56% vs. 5–20%). In the three retrospective studies that evaluated for aspiration events, there was no significant difference in aspiration events, with one study reporting aspiration rates of 4.8 cases per 10,000 in GLP-1 RA users compared to 4.6 cases per 10,000 in nonusers and the remaining two studies reporting one aspiration event in the GLP-1 RA user group and none in the non-user group. In one study that evaluated for regurgitation or reflux by esophageal manometry and pH, there was no significant difference in reflux episodes but a reduction in gastric acidity in the GLP-1 RA user group compared to the non-user group. Conclusions: There is significant variability in the findings reported in the studies, and most of these studies include confounding factors that may influence the association between GLP-1 RAs and an increased risk of aspiration and related events. While GLP-1 RAs do increase residual gastric contents in line with their mechanism of action, the currently available data do not suggest a significant increase in aspiration and regurgitation events associated with their use and the withholding of GLP-1 RAs to reduce aspiration and regurgitation events, as is currently recommended by many major societal guidelines. Large randomized controlled trials (RCTs) may be helpful in further elucidating the impact of GLP-1 RAs on perioperative aspiration risk. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included “GLP-1” or “GLP-1 agonists” combined with “hidradenitis suppurativa” or “acne inversa”. Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS. Full article

A host of anti-hyperglycemic agents are currently available and widely prescribed for diabetes and weight loss management. In patients undergoing surgery, use of these agents poses a clinical challenge to surgeons, anesthesiologists, and other perioperative care providers with regard to optimal timing of discontinuation and resumption of use, as well as possible effects of these agents on physiology and risk of postoperative complications. Here, we provide a comprehensive review of anti-hyperglycemic medications’ effects on physiology, risks/benefits, and best practice management in the perioperative setting. Additionally, we report an illustrative case of small bowel obstruction in a patient taking semaglutide for 6 months prior to an otherwise uncomplicated laparoscopic hysterectomy and bilateral salpingo-oophorectomy. This review is meant to serve not as a replacement of, but rather as a consolidated complement to, various society guidelines regarding perioperative anti-hyperglycemic agent management. Full article

Background: Several GLP-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes (T2DM). Their cardio- and renal-protective effects and their association with substantial weight loss have been evident and progressively expanded their role in the American Diabetes Association (ADA) guidelines, which are endorsed by the European Association for the Study of Diabetes (EASD). The increased demand led to a global shortage. Methods: We utilized a repeated cross-sectional design, drawing data from national prescribing databases, to analyze six GLP-1 RAs: Dulaglutide, Exenatide, Liraglutide, Lixisenatide, Semaglutide, and Tirzepatide. AutoRegressive Integrated Moving Average (ARIMA) models with exogenous variables were applied to assess the trends over time and in different regions. Results: The prescription rates significantly differ between regions. Wales shows the highest prescribing rate for most GLP-1 RAs. The ARIMA models indicated a significant increase in their prescribing rates after the release of the 2022 ADA guidelines (e.g., Dulaglutide: Post-ADA effect of 15.22, 95% CI: [12.97, 17.47]). Following the GLP-1 RA shortages in July 2023, the prescribing rates, particularly for Semaglutide, increased (Shortage effect: 74.36, 95% CI: [71.92, 76.80]). Model diagnostics, including the Akaike Information Criterion (AIC) and Durbin–Watson statistics, confirmed the robustness of these trends. Conclusions: Informed decisions should be made by considering the prescribing trends before and after important events such as the issuing of new guidelines or safety alerts. Full article

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis. Full article

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin–angiotensin–aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were originally developed in the late 1980s as a class of antidiabetic medication. However, research over the past decade has found them to be a safe and effective weight-loss agent, which has led to the approval of GLP-1 RAs such as Semaglutide as a supplement to lifestyle obesity interventions in multiple countries. When Semaglutide has become commercially unavailable, digital weight-loss services (DWLSs) have prescribed a compounded form of the medication—a practice in which health professionals formulate a replica of the commercial medication to serve ongoing patient needs. Although compounding has been relatively common over the past century, prominent medical bodies have argued that compounding a relatively novel medication such as Semaglutide represents a major safety risk. This study retrospectively compared the weight and side effect outcomes of patients from a large Australian DWLS whose lifestyle coaching was supplemented with either compounded or pure Semaglutide (both groups following the same titration schedule). All data were extracted from the service’s central data repository. To be included in the weight loss analysis, patients needed to have received a minimum of four monthly medication orders between June 2023 and May 2024 and have submitted weight data between 90 and 150 days after the arrival of their first order. All patients who received at least one medication order within the same period were included in the side effect analysis. The mean four-month weight loss percentage was statistically lower in the compounded Semaglutide group (N = 923, M = 9.11, SD = ±5.76) compared to those in the pure Semaglutide group (n = 1858, M = 9.87, SD = ±6.46), t (2032) = −3.15, p = 0.0017. A statistically lower proportion of patients in the compounded Semaglutide group (71.61%) reported at least one side effect than patients in the pure Semaglutide group (77.40%) during the study period, X² (1, N = 7683) = 32.32, p < 0.001. When side effects were disaggregated into severity categories, a statistical difference was only observed in mild side effects, X² (1, N = 7683) = 59.16, p < 0.001. A significantly higher rate of patients from the pure Semaglutide group achieved the ten (50.54% vs. 44.64%), X² (1, N = 7683) = 10.34, p < 0.001, and fifteen (21.42% vs. 12.78%), X² (1, N = 7683) = 30.43, p < 0.001, percent weight loss thresholds than patients from the compounded Semaglutide group. The findings indicate that compounded Semaglutide can be used as a component of tightly controlled DWLSs with slightly less effectiveness and but with slightly lower side effect incidence when compared to pure Semaglutide. Full article

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke. Full article

Background/Objectives: Food cravings involve a strong drive to consume palatable foods irrespective of nutritional status. Importantly, cravings contribute substantially to the obesity epidemic. Managing hunger alone is insufficient for weight management as this relates only to homeostatic eating and does not address the complex aetiology of hedonic eating and its crucial role in food cravings. Medical weight management clinics and anti-obesity medication trials do not routinely identify and address food cravings. Methods: We conducted a narrative review of the literature consisting of 115 peer-reviewed articles (original articles and reviews). We included articles focused on food craving pathophysiology, assessment, and management strategies providing contrasts against the current medical model of weight management seen in obesity pharmacotherapy trials as well as the current standard of practise. Results: We outline the neurohormonal and psychological drivers of cravings, which lead to a spectrum of eating behaviours, from comfort food eating to binge eating disorders. We provide an overview of ways of identification and measurement options, including their strengths and weaknesses, and an overview of management strategies and their cravings control efficacy, spanning lifestyle modifications like nutrition and sleep, psychological therapies (i.e., cognitive behavioural therapy [CBT], acceptance-based therapies such as mindfulness) and, last but not least, medications that not only are approved for weight reduction but reduce cravings. Finally, based on these findings, we provide a proposed integrated and iterative model that is able to evolve and adapt to the individual over time in tackling cravings for long-term weight loss maintenance. Conclusions: The findings emphasise the importance of cravings management and provide a synthesis on how cravings can be identified in a medical weight management setting, which can be practically implemented in an integrated iterative model spanning anti-obesity medications that have craving control data to evidence-based lifestyle and psychological interventions. Full article

Background: Glucagon-like peptide receptor agonists (GLP-1 RAs) are associated with delayed gastric emptying and may increase the risk of aspiration due to retained gastric contents. There are no guidelines on peri-endoscopic use of GLP-1 RAs, and real-world outcomes in an ambulatory setting remain unknown. This study reports real-world data from an ambulatory center associated with a large tertiary hospital. Methods: A retrospective review of electronic medical records was conducted for patients who underwent esophagogastroduodenoscopy (EGD) at a hospital-based outpatient center from January to June 2023. Exclusions included non-elective procedures, current opioid use, altered foregut anatomy, and known gastroparesis. All patients were on GLP-1 RAs before endoscopy and followed standard fasting protocols. Adverse event rates were recorded, and patients were divided into cohorts based on GLP-1 RA use. Univariate and multivariate regression analyses identified risk factors for food retention and complications. Results: A total of 1438 patients underwent elective EGD during the study period. Among the 1046 patients included, 73 (7%) were on GLP-1 RAs. The procedure was aborted in four patients (0.4%) due to gastric food retention, with two (50%) on GLP-1 RAs. Independent risk factors for food retention included GLP-1 RA use (OR: 9.19; 95% CI: 2.73–30.8; p = 0.0003) and diabetes (OR 5.6; 95% CI: 1.72–18.2; p = 0.004). Tirzepatide showed the strongest association (p = 0.0056). Factors that did not impact food retention included A1c, BMI, and gender. Protective factors were age (OR 0.96; 95% CI: 0.93–0.99; p = 0.02) and same-day colonoscopy (OR 0.18; 95% CI: 0.06–0.58; p = 0.003). Conclusions: GLP-1 RA use in diabetics increases the risk of retained gastric contents during elective EGD, particularly with tirzepatide, without increasing aspiration risk. Patients undergoing simultaneous colonoscopy had a lower risk of retained gastric contents. Further studies are needed to evaluate the impact of GLP-1 RAs on gastric food retention and procedural risk. Full article