FORXIGA : An Insulin-Independent Approach

Removes Excess Glucose &

Create Multiple Benefit in Type-2 DM

[ Speakers Name ]

FORXIGA is not indicated for the management of obesity.1 Weight change was a secondary endpoint in clinical trials. 1,2
1. FORXIGA. Summary of product characteristics, 2015; 2. Bailey CJ, et al. Lancet 2010;375:222333. ID 384121 / Mar 2019
Diabetes: A Healthcare Tsunami

IDF Diabetes Atlas, 2015

Type 2 diabetes significantly increases risk of complications1,2

1. International Diabetes Federation. Time to Act. 2001. http://www.idf.org/webdata/docs/Diabetes%20and%20CVD.pdf. Accessed February 28, 2012.
2. Seaquist ER. Diabetes. 2010;59:4-5.
Type 2 diabetesCVD is a leading cause of death

Emerging Risk Factors Collaboration. N Engl J Med. 2011;364(9):829-841.

Type 2 diabetesapproximately one-half of
patients are uncontrolled

Wong ND, et al. Persistent undertreatment of cardiovascular risk factors among subjects with type 2 diabetes in the United States 2005-2006. Presented at:
American Diabetes Association 70th Scientific Sessions; June 25-29, 2010; Orlando, FL.
Type 2 diabetesmany therapies are associated with weight
gain over time1,2

1. Inzucchi SE, et al. ADA/EASD Position Statement. Diabetes Care. 2012;35:1-16. Epub 20 April 2012. 2. Mitri J, Hamdy O. Expert Opin Drug Saf. 2009;8(5):573-584.
Type 2 diabetescontrolling multiple parameters is essential

Incremental reductions sustained

over time in HbA1c and other
parameters can benefit the
physical health of patients with
type 2 diabetes1-5

1. Stratton IM, et al. BMJ. 2000;321:405-412. 2. Pi-Sunyer FX. Postgrad Med. 2009;121(5):94-107. 3. Williamson DF, et al. Diabetes Care. 2000;23(10):1499-1504. 4.
Patel A. Lancet. 2007;370(9590):829-840. 5. Pyrl K, et al. Diabetes Care. 1997;20(4):614-620.
Type 2 diabetesguidelines recommend managing multiple
parameters1-5

Although the EASD and ADA Guidelines each set forth specific HbA1C target goals, an ADA/EASD Joint Position
Statement on management of hyperglycemia (2012) recommends that treatment targets be individualized. 6
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes; ESC=Task Force on Diabetes and Cardiovascular Diseases of the
European Society of Cardiology; AACE=American Association of Clinical Endocrinologists; CDA=Canadian Diabetes Association; WHO=World Health Organization.

1. Guidelines for the prevention, management and care of diabetes mellitus. Cairo, Egypt, World Health Organization, 2006. 2. The Task Force on Diabetes and
Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28:88-
136.
3. American Diabetes Association. Diabetes Care. 2012;35(suppl 1):S4-S10. 4. Handelsman Y, et al. American Association of Clinical Endocrinologists Medical
Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(suppl 2):1-53. 5. Canadian Diabetes
Association Clinical Practice Guidelines Expert Committee. Can J Diabetes. 2008;32(suppl 1):S1-S201. 6. Inzucchi SE, et al. ADA/EASD Position Statement. Diabetes
Care. 2012;35:1-16.
The need for a pathway that acts
independently of insulin in
type 2 diabetes
Multiple Defects Contribute
to the Pathophysiology of T2DM1
Glucose Insulin
production secretion

Glucagon Glucose
secretion uptake
Chronic
Hyperglycemia

Incretin
Lipolysis
effect

Glucose Neurotransmi
reabsorption tter function

To help improve glycemic control, treatments with complementary

mechanisms of action should be considered to be used in combination2
T2DM=type 2 diabetes mellitus.
1. DeFronzo RA. Diabetes. 2009;58:773-795.
2. Garber AJ et al. Endocr Pract. 2013;19:536-557.
Type 2 diabetescharacterized by insulin resistance and -
cell dysfunction1-4

1. Ramlo-Halsted BA, et al. Prim Care. 1999;26(4):771-789. 2. Piya MK, et al. Br J Clin Pharmacol. 2010;70(5):631-634. 3. DeFronzo RA. Med Clin N Am.
2004;88(4):787-835. 4. Stratton IM, et al. BMJ. 2000;321:405-412.
Continuous Glucose Reabsorption Perpetuates the Cycle of
Glucotoxicity in Patients With Type 2 Diabtes13
Reabsorption
Peripheral glucose uptake of filtered glucose back
into the bloodstream
via SGLT2

Type 2
Diabetes:
Chronic
Hyperglyce
mia

Prolonged hyperglycemia, exacerbated by continued glucose reabsorption,

contributes to a vicious cycle of glucotoxicity in the progression of type 2
diabetes
SGLT=sodium-glucose cotransporter.
1. DeFronzo RA. Diabetes. 2009;58:773-795.
2. Gerich JE. Diabet Med. 2010;27:136-142.
3. Poitout V et al. Endocr Rev. 2008;29:351-366.
Insulin-dependent pathways: organs and tissues
Glucose levels are managed in the body partly by insulin-dependent pathways
involving multiple organs and tissues1-6

Organ Insulin-dependent pathways Treatment

cells secrete insulin in response to increasing blood SU, DPP4 inh, Glinid
glucose levels
The insulin accelerates the transport of glucose into
cells, reducing blood glucose levels
Insulin also reduces hyperglycemia by promoting
energy storage through stimulating the conversion of
glucose into glycogen (glycogenesis) and through
promoting lipogenesis

Insulin binding to insulin receptors promotes the Metformin, TZD

appearance on the cell membrane of glucose transporter 4
(GLUT4) molecules, facilitating the uptake of glucose into
the cells

Insulin regulates blood glucose levels by suppressing Metformin, TZD

hepatic glucose output and increasing postprandial
glucose storage in the form of glycogen

Insulin helps in the synthesis and storage of excess Metformin, TZD

glucose in the form of triglycerides

Incretin hormones secreted by the gut in response to a DPP4 inh

meal promote glucose-mediated insulin secretion and
suppress glucagon levels

1. DeFronzo RA. Med Clin N Am. 2004;88(4): 787-835. 2. Guyton AC. Textbook of Medical Physiology. 7th ed. Philadelphia, PA: WB Saunders Company; 1986.
3. Uldry M, Thorens B. Eur J Physiol. 2004;447(5):480-489. 4. Guyton AC. Textbook of Medical Physiology. 11th ed. Philadelphia, PA: WB Saunders Company;
2006. 5. Drucker DJ, Nauck MA. Lancet. 2006;368(9548):1696-1705. 6. Schirra J, et al. Gut. 2006;55(2):243-251.
An insulin-independent pathwayrenal SGLT21,2

1. Rajesh R, et al. Int J Pharma Sci Res. 2010;1(2):139-147. 2. Marsenic O. Am J Kidney Dis. 2009;53(5):875883.
 The role of the renal SGLT
pathway in glucose balance
In normal renal glucose handling, 90% of glucose is
reabsorbed by SGLT214
Majority of glucose
is reabsorbed by
SGLT2 (90%)

Proximal tubule

Remaining
glucose is
SGLT2
Glucose reabsorbed by
Glucose filtration SGLT1 (10%)
Minimal to
no glucose
excretion
SGLT, sodium-glucose co-transporter 2.
Adapted from: 1. Wright EM. Am J Physiol Renal Physiol 2001;280:F1018; 2. Lee YJ, et al. Kidney Int Suppl 2007;106:S2735; 3. Hummel CS, et al. Am J Physiol Cell Physiol 2011;300:C1421;
4. Marsenic O. Am J Kidney Dis 2009;53:87583.
SGLT and GLUT transporters facilitate insulin independent
reabsorption of filtered glucose in the proximal tubule
Tissue
S1 proximal
reabsorption
tubule lumen
(filtrate)
ATPase SGLT2
SGLT 2
Glucose
Low affinity
1 Na+
GLUT 2
High capacity

Tissue
reabsorption
S3 proximal
tubule lumen
(filtrate) SGLT 1 Glucose
ATPase
SGLT1
2 Na+ High affinity
GLUT 1 Low capacity

17
GLUT, glucose transporter; SGLT, sodium-glucose co-transporter.
Adapted from: Wright EM. Am J Physiol Renal Physiol 2001;280:F1018.
FORXIGA inhibits SGLT2 and removes excess glucose in the
urine independently of insulin
SGLT2
Reduced glucose
reabsorption
FORXIGA

Proximal tubule

Increased urinary
Increased urinary
excretion
excretion of excess
of excess
SGLT2 Glucose glucose
glucose (~70 g/day,
(~70 g/day,
filtration corresponding
corresponding toto
Glucose 280kcal/day*
kcal/day*)1)
280
FORXIGA

By inhibiting SGLT2, FORXIGA removes glucose and associated calories

FORXIGA is >1400-times more selective for SGLT2 versus SGLT1
*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with
Type 2 diabetes.
FORXIGA. Summary of product characteristics, 2015.
FORXIGA lowers HbA1c to deliver multiple benefits

Glycaemic Weight loss Blood pressure

control reduction
FORXIGA:1 Urinary excretion of ~70 g FORXIGA is associated with
Acts independently of insulin glucose/day with FORXIGA significant reductions in SBP,
mechanisms to reduce HbA1c via corresponds to loss of 280 which is likely to be due in part
the kidney kcal/day*1 (1 g glucose = to the effect of increased
~4 kcal) diuresis1
Works regardless of -cell
function 1 lb of body fat equates to
Has a low propensity for ~3500 calories2
hypoglycaemia

FORXIGA is not indicated for the management of weight loss or high blood pressure. Weight change was a secondary endpoint, and blood pressure change was
primarily assessed as a safety or exploratory efficacy endpoint in clinical trials.
*Increases urinary volume by only ~1 additional void/day (~375 mL/day) in a 12-week study of healthy subjects and patients with Type 2 diabetes.1 (
FORXIGA is not recommended for use in patients receiving loop diuretics or who are volume depleted, e.g. due to acute illness (such as gastrointestinal illness). 1

CV, cardiovascular; SBP, systolic blood pressure; XR, extended release.

1. FORXIGA. Summary of product characteristics, 2015; 2. Calories per hour.com. Available at: www.caloriesperhour.com/tutorial_pound.php.
Last accessed April 2016.
FORXIGA is supported by a wealth of real-world experience
and clinical trial data

>20,000 4-year >900,000

patients in patients treated
data available3
ongoing trials1,2 worldwide*4
(FORXIGA
SmPC 2015)
(/p1/table;p4/table;
p5/figure)

*Data are estimates derived from the use of information under the licence from the IMS Health Total Patient Tracker, December 2015; Cegedim Strategic Data, Longitudinal
Patient Databases, December 2015; IMS NPA Market Dynamics Data, April 2014December 2015; IMS Lifelink, May 2015.
1. EMDAC background document. Available at: www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/
endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed April 2016; 2. ClinicalTrials.gov. Identifier: NCT01730534. Available online at:
ClinicalTrials.gov (updated 30 September 2014); 3. Del Prato S, et al. Diabetes Obes Metab 2015;17:58190; 4. Data on file (IMS Health Total Patient Tracker, December
2015; Cegedim Strategic Data, Longitudinal Patient Databases, December 2015; IMS NPA Market Dynamics Data, April 2014December 2015; IMS Lifelink, May 2015).
Shown Significant Efficacy from 1st Week of Treatment

Fasting plasma glucose (FORXIGA PI):

Treatment with dapagliflozin 10 mg as an add-on to either metformin, glimepiride, or pioglitazone resulted in
statistically significant reductions in fasting plasma glucose (-1.64 to -1.31 mmol/l [-29.6 to -23.5 mg/dl])
compared to placebo (-0.33 to -0.11 mmol/l [-6.0 to -2.0 mg/dl]). This effect was observed at Week 1 of
treatment and maintained in studies extended through Week 102
Bailey et al. Lancet 2010; 375: 222333
Forxiga Indonesia PI 2015
 Consistent Decreases in Fasting Plasma Glucose at 24
weeks1,2,3
Add On to Metformin1 Add On to Sulfonilurea2 Add On to TZD3
Met+ Met+ SU+ SU+ TZD+ TZD+
Forxiga 10mg Placebo Placebo
FPG Adjusted mean Changed from Baseline

Forxiga 10mg Placebo Forxiga 10mg

0

-5 -1.8 mg/dl
-5.4 mg/dl
-5.4 mg/dl
-10
p< 0.0001 p< 0.0001 p< 0.0001

-15

-20

-25 -23.4 mg/dl

-30
-28.8 mg/dl -28.8 mg/dl

-35

1. Bailey CJ, et al. Lancet 2010;375:2223-33; 2. Strojek K, et al. Diabetes Obes Metab 2011;13:928-38; 3. Rosenstock J, et
al. Diabetes Care, Volume 35, July 2012
Consistent Decreases Post Prandial Glucose after 2 hours at
24 weeks1,2

Add-on Add on +
to Pio1 SU2
308 321.3

5 mg 10 mg Pbo

n=139

n=141 n=140

Forx 5 P=0.0007 vs plac Both P<0.0001 vs plac

Forx 10 P<0.0001 vs plac

1. Rosenstock J, et al. Diabetes Care, Volume 35, July 2012

2. Strojek et.al. Diabetes, Obesity and Metabolism 13: 928938, 2011.
FORXIGA Consistent reductions in HbA1c in patients as add
on therapy at 24 weeks
Add-on to metformin1 Add-on to a Add-on to Pio3
0.5 0.5 SU2 0.5

Met+ SU+ Pio+

Mean change in HbA1c(%)

SU+
Forxiga Met+ Forxiga Placebo Forxiga Pio+
10mg Placebo 10mg 10mg Placebo
0.0 0.0 0.0

0.13
0.30
-0.5 -0.5 -0.5 0.42

0.84* 0.82*
-1.0 -1.0 -1.0
0.97*

P< 0.0001 P< 0.0001 P< 0.0001

CI 95% -98 to 0.70) CI 95% -0.88 to -0.51) CI 95% -33.1 to 3.0)
-1.5 -1.5 -1.5

Baseline HbA1c: Baseline HbA1c: Baseline HbA1c:

8.06% 8.07% 8.53%

*Statistically significant vs placebo using Dunnetts correction. SU, sulphonylurea.

1. Bailey CJ, et al. Lancet 2010;375:222333;
2. Strojek K, et al. Diabetes Obes Metab 2011;13:92838; 4. Wilding JPH, et al. Ann Intern Med 2012;156:405
15.
3. Rosenstock J, et al. Diabetes Care, Volume 35, July 2012
.
Consistent reductions in HbA1c in patients with baseline
HbA1c 9%
Add on to Add on to Add on
metformin1 SU1 to Pio1
Met+ SU+ Pio+
Forxiga Met+ Forxiga SU+ Forxiga Pio+
10mg Placebo 10mg Placebo 10mg Placebo

-0.5

-1.57
(24 weeks)

9.05%
9.7% 9.6%
NR, not reported.
1. Katz A, et al. Diabetes 2014;63(Suppl. 1):A284.
Superior HbA1c reduction with Forxiga compare with
a DPP-4 Inhibitor9
Baseline (%) [mmol/mol] 9.03 [75.2] 8.87 [73.4]
na 143 151

SAXA+MET DAPA+MET
Adjusted mean (95% CI) change

0.0
from baseline in HbA1c (%)

-0.5

-1.0
0.88

1.20
-1.5

0.32% (0.54%, 0.10%)

P=0.0040

aNumber of randomized patients with non-missing baseline values and Week 24 values last observation carried forward (LOCF)
CI, confidence interval; DAPA, dapagliflozin; HbA1c, glycated haemoglobin; MET, metformin; SAXA, saxagliptin

Dapagliflozin Versus Saxagliptin as Add-on Therapy in Patients T2D diabetes Who Have Inadequate Glycemic Control with Metformin: a Post Hoc Analysis.
Efficacy outcomes (adjusted change from baseline at 24 weeks)

C. FPG; D. 2h-PPG; n is the number of randomized patients with non-missing baseline and Week 24 LOCF values. BL, baseline; CI,
confidence interval; DAPA, dapagliflozin; FPG, fasting plasma glucose; MET, metformin; 2h-PPG, 2-hour postprandial glucose; SAXA,
saxagliptin Rosenstock J, et al. WCIRDC 2016 Poster 99
DPP4 Inh Had Comparable HbA1c Reduction

HbA1c reduction in week 18

Scheen AJ et al, Diabetes Metab Res Rev 2010; 26: 540549.
DPP4 Inh Had Comparable
HbA1c Reduction

HbA1c reduction in week 24

**p < 0.01 for mean change from baseline in Vildagliptin, Saxagliptin and Sitagliptin
FORXIGA: Reductions in HbA1c were sustained over time
Primary endpoint
24 weeks Placebo + metformin
0.2 (Mean baseline HbA1c 8.13%)
(n=133) +0.02%
Adjusted mean change from

0.0 (n=132)
(95% Cl,
0.20 to 0.23%;
baseline HbA1c (%)

n=57)
-0.2
0.80%
-0.4 difference

FORXIGA 10 mg + metformin
-0.6 (Mean baseline HbA1c 7.95%)
0.78%
-0.8 (95% Cl,
0.97 to 0.60%;
n=57)
-1.0
0 8 16 24 37 50 63 76 89 102
Study week P<0.0001

Data are mean change from baseline after adjustment for baseline value. Data after rescue are excluded. Analyses were obtained by longitudinal repeated measures analyses.
CI, confidence interval.
1. Bailey CJ, et al. Bailey et al. BMC Medicine 2013, 11:43.
FORXIGA as add-on to
metformin versus SU: Comparable HbA1c reductions over 4 years1

At 52 week primary endpoint FORXIGA was non-inferior to glipizide: Both resulted in HbA1c reductions of 0.52%2

FORXIGA is not indicated for the management of obesity.3 Weight change was a secondary endpoint in clinical
trials.3,4
Data are adjusted mean change from baseline derived from a longitudinal repeated measures mixed model.
A Phase III, multicentre, randomised, double-blind, parallel-group, 52-week, glipizide-controlled, non-inferiority study with a double-blind extension to evaluate the
efficacy and safety of FORXIGA
10 mg + metformin (15002000 mg/day) versus glipizide + metformin (15002000 mg/day) in patients with inadequate glycaemic control (HbA1c >6.5% and 10%)
on metformin alone.1
*The risk of hypoglycaemia with dapagliflozin is dependent on the type of background therapy used.3
1. Del Prato S, et al. Presented at the 73rd American Diabetes Association Scientific Sessions, Chicago, USA. 2125 June 2013. Abstract 62-LB; 2. Nauck MA, et
al. Diabetes Care 2011;34:201522. 3. FORXIGA. Summary of product characteristics, 2015; 4. Bailey CJ, et al. Lancet 2010;375:222333.
 Insulin Secretion And
Beta-cell Function Were Significantly Improved With Dapagliflozin
To examine the glucotoxicity hypothesis, dapagliflozin was used to lower the plasma glucose
concentration. The effect of this intervention on beta-cell function was examined using a euglycemic
hyperinsulinemic clamp
Insulin Secretion and Beta-cell Function
(measured As c-pep0120/G0120 IR after 2 Weeks)
0.30 *
c-pep0120/G0120

0.25

c-pep0120/G0120
0.05 * 0.20

0.04 0.15

0.03 0.10

0.02 1/TGD 0.05

0.01 0
Dapa PlaceboDapa Placebo Dapa PlaceboDapa Placebo
Baseline Treatment Baseline Treatment
Insulin Secretion Beta cell Function
Merovci A, et al. J Clin Endocrinol Metab 100: 19271932, 2015 *, P < .05 vs baseline and vs placebo
Beta-cell Glucose Sensitivity Significantly Increased
With Dapagliflozin
Beta-cell glucose sensitivity measured with the Mari model
750
P<0.01
Insulin Secretory Rate

Dapa
(pmol/min*mM)

500

Baseline
250

0
10 15 20 25

Plasma Glucose Concentration (mM)

Merovci A, et al. J Clin Endocrinol Metab 100: 19271932, 2015
FORXIGA: Additional benefit of weight loss a cross
broad range of treatments
Add on to Add on to Add on to
metformin1 SU2 Pio3

1.64

FORXIGA 10 mg
-0.14 Placebo

(24 weeks)
84.8 86.4

FORXIGA is not indicated for the management of obesity.6 Weight change was a secondary endpoint in clinical trials. 2,6
*Statistically significant versus placebo using Dunnetts correction (p<0.0001); Statistically significant versus placebo after sequential testing procedure (p<0.0001);
Statistically significant versus placebo (p<0.0001); Statistically significant versus placebo (p<0.001). Adjusted mean change from baseline using analysis of

covariance, excluding data after rescue (last observation carried forward).

1. Bailey CJ, et al. Lancet 2010;375:222333; 2. Strojek K, et al. Diabetes Obes Metab 2011;13:92838; 3. Rosenstock J, et al. Diabetes Care, Volume 35, July 2012
 Efficacy outcomes (adjusted change from baseline at
24 weeks)

Both dapagliflozin and DPP-4

Inh demonstrated efficacy;
however, dapagliflozin
significantly reduced weight
more than DPP-4 Inh

A. HbA1c; B. body weight. n is the number of randomized patients with non-missing baseline and Week 24 LOCF values. BL,
baseline; CI, confidence interval; DAPA, dapagliflozin; FPG, fasting plasma glucose; MET, metformin; 2h-PPG, 2-hour
postprandial glucose; SAXA, saxagliptin. Rosenstock J, et al. WCIRDC 2016 Poster 99
FORXIGA as add-on to metformin versus placebo:
Additional benefit of weight loss sustained over 2 years1

Double blind Extension

Sample size (including data after rescue)

FORXIGA 133 121 113 95
+
metformin
Placebo
+ 136 120 105 73
metformin
FORXIGA is not indicated for the management of obesity.3 Weight change was a secondary endpoint in clinical trials.2,3
Data are mean change from baseline after adjustment for baseline value. Data after rescue are excluded. Analyses were obtained by longitudinal repeated measures analyses. A Phase
III, multicentre, randomised, double-blind, placebo-controlled, parallel-group, 24-week clinical study with a 78-week, double-blind extension in adult patients with Type 2 diabetes who had
inadequate glycaemic control (HbA1c 7% and 10%) on metformin alone. Primary endpoint: HbA1c reduction at 24 weeks.1,2
CI, confidence interval.
1. Bailey CJ, et al. BMC Med 2013;11:43; 2. Bailey CJ, et al. Lancet 2010;375:222333; 3. FORXIGA. Summary of product characteristics, 2015.
 FORXIGA: Additional benefit of weight loss sustained over
time1
Glipizide + metformin
(n=401)
2.0 Mean baseline weight 87.6 kg
1.5 +1.36 kg
Adjusted mean change from

1.0 (95% Cl,

0.88 to 1.84 kg;
0.5
baseline weight (kg)

n=211)
0.0
-0.5
-1.0 5.06 kg difference
(95% Cl, 5.73 to 4.4 kg)
-1.5
-2.0 FORXIGA 10 mg + metformin
-2.5 (n=400)
-3.0
Mean baseline weight 88.4 kg 3.70 kg
(95% Cl,
-3.5 4.16 to 3.24 kg;
n=234)
-4.0
0 6 12 18 26 34 42 52 65 78 91 104
Study week

Data are adjusted mean change from baseline and 95% CI derived from a repeated measures mixed model.
1. Nauck MA, et al. Diabetes Care 2011;34:201522;
FORXIGA as add-on to metformin versus SU:
Additional benefit of weight loss sustained over 4 years1

FORXIGA is not indicated for the management of weight loss. Weight change was a secondary endpoint in clinical trials.
Data are adjusted mean change from baseline derived from a longitudinal repeated measures mixed model.
A Phase III, multicentre, randomised, double-blind, parallel-group, 52-week, glipizide-controlled, non-inferiority study with a double-blind extension to evaluate the
efficacy and safety profile of FORXIGA 10 mg + metformin (15002500 mg/day) versus glipizide + metformin (15002500 mg/day) in patients with inadequate glycaemic
control (HbA1c >6.5% and 10%) on metformin alone. CI, confidence interval.
1. Del Prato S, et al. Diabetes Obes Metab 2015;17:58190; 2. Nauck MA, et al. Diabetes Care 2011;34:201522
 Reduction in total body weight with FORXIGA is principally
due to reduction in fat mass1,2
FORXIGA demonstrated a significant reduction in fat mass rather than lean tissue or fluid
loss sustained up to 102 weeks2

P<0.0001 P<0.0001
95% CI -2.84 to -1.31 95% CI -2.51 to -0.96

1 2

FORXIGA is not indicated for the management of obesity. 2 Weight change was a secondary endpoint in clinical trials. 2,3
*Data are adjusted mean change from baseline derived from a longitudinal repeated-measure mixed model and include data after rescue therapy.
1. Bolinder J, et al. Diabetes Obes Metab 2012;16:15969; 2. Bailey et al. BMC Medicine 2013, 11:43.
MR substudy: VAT and SAT at Week 24
VAT volume (cm3) SAT volume (cm3)
Placebo FORXIGA 10 mg Placebo FORXIGA 10 mg
+ metformin + metformin + metformin + metformin
0

-50
Mean change from baseline (cm3)

39.2

-100
121.4
-150

-200

P = 0.0084 P = 0.0385
-250

-300
297.5 306.4
-350
MR, magnetic resonance; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.
Bolinder J, et al. J Clin Endocrinol Metab 2012;97:102031.
 FORXIGA: Adjusted mean change in waist circumference
(cm) from baseline at Week 24
Placebo + metformin FORXIGA 10 mg + metformin
(n=91) (n=89)
0
Baseline 104.5 Baseline 105.6
0.5
Change in waist circumference

1
(cm) (SE)

1.5 0.99

2.5

3
2.51*
3.5
*p=0.0143.
SE, standard error.
Bolinder J, et al. J Clin Endocrinol Metab 2012;97:102031.
FORXIGA added to
various antihypertensives: Additional benefit of significant SBP reduction13
Co-primary endpoints were change from baseline to Week 12 in SBP and HbA1c (Weber 2013 abstract 2095)(/p1/column1) (Weber 2013 abstract 2097)(/p1/column1)

At Week 12, FORXIGA added to background antidiabetic agents reduced placebo-corrected HbA1c by 0.46% and
0.61% in patients administered ACEi/ARB or ACEi/ARB + additional anti-HTN therapy, respectively1,2
(Weber 2013 abstract 2095)(/p1/figure3) (Weber 2013 abstract 2097)(/p1/figure3)

Depending on baseline HbA1c, 6475% of patients achieved a decrease of 5 mmHg in SBP with FORXIGA 10 mg3
FORXIGA is not indicated for the management of high blood pressure. Blood pressure change was primarily assessed as a safety or exploratory efficacy endpoint in
clinical trials.
ACEi, angiotensin-converting-enzyme inhibitors; anti-HTN, antihypertensive treatment; ARB, angiotensin receptor blocker; CI, confidence interval;
SBP, systolic blood pressure.
1. Weber MA, et al. Poster presented at Annual Meeting of the American Heart Association, Dallas, Texas, USA. 16-20 November 2013; Abstract 2095; 2. Weber MA et al. Poster
presented at Annual Meeting of the American Heart Association, Dallas, Texas, USA. 16-20 November 2013; Abstract 2097;
3. Moran J, et al. Presented at the Annual Scientific Sessions of the American Diabetes Association, Boston, USA. 59 June 2015. Poster 1198-P.
FORXIGA as add-on
to metformin: Reductions in SBP are sustained over 4 years1
The primary endpoint was change from baseline to Week 208 in HbA 1c, with SBP and weight change as
secondary endpoints (Del Prato 2015)(/p2/para5)
At Week 208, FORXIGA + metformin reduced HbA1c by 0.10% versus an increase of +0.20% with SU + metformin
(Del Prato 2015)(/p3/para2)

FORXIGA is not indicated for the management of high blood pressure. Blood pressure change was primarily assessed as a safety or exploratory efficacy endpoint in clinical trials.
A Phase III, multicentre, randomised, double-blind, parallel-group, 52-week, glipizide-controlled, non-inferiority study with a double-blind extension to evaluate the efficacy and safety profile of FORXIGA
10 mg + metformin (15002500 mg/day) versus glipizide + metformin (15002500 mg/day) in patients with inadequate glycaemic control (HbA1c >6.5% and 10%) on metformin alone.1 (Del Prato
2015)(/p1/para1;p2/para1;p2/para2)
CI, confidence interval, SBP, systolic blood pressure; SU, sulphonylurea.
1. Del Prato S, et al. Diabetes Obes Metab 2015;17:58190.
FORXIGA: UTIs and genital infections

Placebo-controlled pool (short-term)2

Events (%)
FORXIGA 10 mg Placebo
(N=2360) (N=2295) A comparable safety profile was
UTIs 110 (4.7) 81 (3.5) also seen in real-world
observational studies36
Genital infections 130 (5.5) 14 (0.6)

Most genital infections* and UTIs were mild to moderate in intensity, rarely led to
discontinuation of FORXIGA and were generally resolvable with a single course of
standard treatment1
Pyelonephritis was uncommon and occurred at a similar frequency to control1
*Genital infection includes the preferred terms: Vulvovaginal mycotic infection, vaginal infection, balanitis, genital infection fungal, vulvovaginal candidiasis,
vulvovaginitis, balanitis candida, genital candidiasis, genital infection, genital infection male, penile infection, vulvitis, vaginitis bacterial and vulval abscess.
Data for dapagliflozin only
UTI, urinary tract infection.
1. FORXIGA. Summary of product characteristics, 2015; 2. EMDAC background document. Available at:
www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last
accessed April 2016; 3. McGovern AP, et al. Br J Diabetes Vasc Dis 2014;14:13843; 4. Hitke ZZ, et al. Diabetes Medicine 2015;32(Suppl. 1):29 (Abstract
P471); 5. Bellan Kannan RB. et al. Diabetic Medicine 2015;32(Suppl. 1):29 (Abstract P470); 6. Down S, et al. Diabetes Medicine 2015;32(Suppl. 1):29
(Abstract P246).
Genital Infection: Asian Population
n / N (%) of patients
Placebo controlled pool, ST period, Placebo controlled pool, ST + LT
30-MSU period, 30-MSU
Dapa 10 mg Placebo Dapa 10 mg Placebo
N = 2360 N = 2295 N = 2026 N = 1956

Total Patients with an 130 / 2360 (5.5) 81 / 2295 (0.6) 156 / 2026 (7.7) 19 / 1956 (1.0)
event
White 111 / 1976 (5.6) 11 / 1930 (0.6) 138 / 1739 (7.9) 15 / 1695 (0.9)
Black/African American 9 / 81 (11.1) 2 / 73 (2.7) 10 / 66 (15.2) 3 / 61 (4.9)

Asian 6 / 209 (2.9) 1 / 206 (0.5) 5 / 131 (3.8) 1 / 120 (0.8)

Other 4 / 94 (4.3) 0 / 86 3 / 90 (3.3) 0 / 80

Source: Internal Data submitted to BPOM

 FORXIGA:
Other selected adverse events
Adverse event Details

Serum electrolytes FORXIGA has no clinically relevant impact on serum electrolytes1

No increased risk of hyperkalaemia with FORXIGA
Lipids Small mean changes from baseline in fasting lipid levels were observed with
FORXIGA 10 mg1
Haematocrit Small dose-dependent changes from baseline were observed in the
haematocrit (up to 2.32% mean increase for FORXIGA 10 mg)1
Caution in patients with already elevated haematocrit is warranted 2

Hepatic safety No mean increases from baseline or imbalances in liver laboratory tests for
FORXIGA versus control1
The proportion of patients with elevated laboratory values for ALT, AST,
total bilirubin and ALP was similar in the FORXIGA and
control groups1

Bone fractures The proportions of patients with fractures were small and balanced for
FORXIGA versus placebo1
Drug-to-drug No known clinically relevant drug-to-drug interactions with FORXIGA2
interactions

Please see full prescribing information for adverse event data.

ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase.
1. EMDAC background document. Available at:
http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last
accessed September 2014.
2. FORXIGA. Summary of product characteristics, 2015.
 Events of volume depletion* were infrequent but more common in
patients treated with FORXIGA than placebo

Placebo-controlled pool Placebo-controlled pool

(short term)1,2 (short term + long term)2

FORXIGA FORXIGA
Placebo Placebo
10 mg 10 mg

N=2360 N=2295 N=2026 N=1956

Events, n (%)
27 (1.1) 17 (0.7) 38 (1.9) 27 (1.4)

Serious events occurred in <0.2% of patients and were comparable between groups2
Urinary volume increases were sustained at 12 weeks and amounted to approximately 375 mL/day1
(approximately equivalent to a can of soft drink)

FORXIGA is not recommended for initiation of therapy in patients who are volume depleted. Elderly patients may be at a greater
risk for volume depletion and are more likely to be treated with diuretics. In subjects 65 years of age, a higher proportion of
subjects treated with FORXIGA had adverse reactions related to volume depletion. Therapeutic experience in patients 75 years
and older is limited. Initiation of FORXIGA therapy in this population is not recommended. Temporary interruption of FORXIGA is
recommended for patients who develop volume depletion until the depletion is corrected.1,2

*Including dehydration, hypovolaemia or hypotension.

1. FORXIGA. Summary of product characteristics, 2014; 2. EMDAC background document. Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/
drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf. Last accessed September 2014.
SGLT2 inhibition requires sufficient kidney function

The efficacy of SGLT2 inhibitors is

dependent on renal function1,2
Efficacy is reduced in patients who have
moderate renal impairment and likely absent
in patients with severe renal impairment
FORXIGA is not recommended for use in
patients with moderate-to-severe renal
impairment*1
In a pooled safety profile analysis, patients
treated with FORXIGA demonstrated stable
eGFR over 2 years3
*FORXIGA can be used in patients with normal or mildly impaired renal function (eGFR 60 mL/min/1.73 m 2), but is not recommended for use in patients
with moderate-to-severe renal impairment (CrCL <60 mL/min or eGFR <60 mL/min/1.73 m 2).1 (
CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate; SGLT2, sodium-glucose co-transporter-2.
1. FORXIGA. Summary of product characteristics, 2015; 2. Inzucchi SE, et al. Diabetes Care 2015;38:1409; 3. Kohan DE, et al. J Nephrol 2016. DOI 10.1007/s40620-016-
0261-1
 FORXIGA: Renal function guidance
The efficacy of all SGLT2 inhibitors is dependent on renal function14

FORXIGA is not recommended for

FORXIGA can be used in1
use in1

patients with moderate-to-severe

patients with normal or mildly impaired
renal impairment (CrCl <60 mL/min or
renal function (eGFR 60 mL/min/1.73 m2)
eGFR <60 mL/min/1.73 m2)

The monitoring of renal function is recommended as part of HOLISTIC Diabetes

Management1

Prior to initiation of SGLT2 inhibitor and at least yearly thereafter as part of Diabetes Management
Prior to initiation of concomitant medicinal products that may reduce renal function and periodically
thereafter
For renal function approaching moderate renal impairment, at least two to four times
per year. If renal function falls below CrCl <60 mL/min or eGFR <60 mL/min/1.73 m 2, FORXIGA treatment
should be discontinued

CrCL, creatinine clearance.

1. FORXIGA. Summary of product characteristics 2014; 2. Canagliflozin. Summary of product characteristics 2013; 3. Empagliflozin. Summary of product characteristics 2014;
4. Gilbert RE. Kidney Int 2013; Epub ahead of print.
Kidney function in
consideration Due to MOA of FORXIGA in Kidney
In patients FORXIGA renal function remained stable over time until 102 weeks 1
Side effects associated with increased creatinine reported 3.2% of patients FORXIGA vs 1.8% placebo 1
FORXIGA (creatinine are reversible and are rarely associated with clinically significant changes vs baseline) 1
Mean change in eGFR from

FORXIGA 10 mg
baseline (mL/min/1.73 m2)

Placebo

Number of patients
FORXIGA 2026 1697 1655 1777 1600 1663 712 692 656 627
Placebo 1955 1629 1570 1671 1513 1558 605 585 551 521

*Adverse drug reactions related to increased creatinine were grouped (e.g. decreased renal creatinine clearance, renal impairment, increased blood creatinine and
decreased glomerular filtration rate).
eGFR, estimated glomerular filtration rate; LT, long-term; MDRD, modification of diet in renal disease; MoA, mechanism of action; ST, short-term.
1. EMDAC background document.
Available at: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm378079.pdf
Last accessed September 2014;
FORXIGA as add-on to metformin versus SU:
Lower risk of hypoglycaemia at 4 years
100
90
80 ~10X
Patients with 1 episode

lower
of hypoglycaemia (%)

incidence
70
60
51.5%
(n=408)
50
40
30
20 5.4%
10 (n=406)
0
FORXIGA 10 mg Glipizide
+ metformin + metformin

208 weeks
P value is not obtain from citation source

Del Prato S, et al. Presented at the 73rd American Diabetes Association Scientific Sessions, Chicago, USA. 2125 June 2013. Abstract 62-LB.
FORXIGA as add-on to metformin versus SU:
Lower risk of hypoglycaemia during Ramadan
100
90
Any reported symptomatic or
documented hypoglycaemia*

80
70
~4X lower
60 incidence

50
28.8%
40 (n=52)
30
20 6.9%
10 (n=58)
0
FORXIGA 10 mg Sulphonyl Urea (SU)*
+ metformin + metformin

4 weeks of Ramadan
P=0.002

*SU= glimepiride, gliclazide or glibenclamide

Wan Juani et al. Diabetes, Obesity and Metabolism 2016 doi:10.1111/dom.12649

 Meta-analysis data:
The results suggest the potential for a beneficial CV effects
A meta-analysis of CV events among 21 Phase IIb/III trials, showed no increase in the primary composite endpoint of
CV death, stroke, MI and hospitalisation for UA with FORXIGA at 50 months 1
Kaplan-Meier estimate for primary endpoint (MACE + UA), all Phase IIb and III pool

Control

Dapagliflozin 10 mg

FORXIGA

No increased risk for early (in the first 30 days) CV events with FORXIGA2
No increased risk of CV death or hospitalisation for heart failure with point estimates favourable towards FORXIGA (HR=0.70;
95% CI, 0.36 to 1.36 and HR=0.36; 95% CI, 0.16 to 0.84, respectively)1

CI, confidence interval, CV, cardiovascular; HR, hazard ratio; MACE, major adverse cardiovascular event; MI, myocardial
infarction; UA, unstable angina.
1. Sonesson C, et al. Cardiovasc Diabetol 2016;15:37; 2. List J, et al. Circulation 2014;130:A16682.
Recent meta analysis with Dapagliflozin (Sonesson et al)
21 Phase IIb/III trials, n=9339 (DAPA n=5936; Control n=3403)

DAPA
Meta Analysis* DAPA
Favors
HR vs Control
DAPA Control
(95% CI)
n/N Event rate/ Event rate/
DAPA 100 p-y Control 100 p-y

0.79
MACE plus UA 95/5699 1.46 81/3240 2.15
(0.58, 1.1)

0.77
MACE 72/5418 1.15 62/3101 1.69
(0.54, 1.1)

0.70
CV death 20/3825 0.37 18/2200 0.59
(0.36, 1.36)

0.57
MI 30/5244 0.48 33/3014 0.91
(0.34, 0.95)

1.00
Stroke 25/4227 0.45 18/2412 0.57
(0.54, 1.86)

Hospitalization for 0.36

10/2576 0.15 16/1780 0.41
heart failure (0.16, 0.84)

0.10 1.00 2.0

*All Phase 2b and 3 Pool, ST + LT -30MU; Stratified by study; Only trials with at least one positively adjudicated event included in analysis; Cox Proportional
Hazards model.
n= number of patients with an event; N= number of patients in treatment group; CV=cardiovascular; DAPA=dapagliflozin; HR=hazard ratio; CI=confidence interval;
MACE=Major Adverse Cardiovascular Event; UA=unstable angina; MI=myocardial infarction.

Sonesson C et al. Cardiovasc Diabetol. 2016;15:37.

 Recent meta-analysis data suggest net protection against
cardiovascular events with SGLT2 inhibitors (Wu et al)
SGLT2 Control Relative SGLT2 Control Relative
inhibitor (n/N) risk inhibitor (n/N) risk
(n/N) (95% CI) (n/N) (95% CI)

MACE
Canagliflozin 104/6396 2/3403
62/3403 1.02 (0.741.42) Non-fatal stroke
Canagliflozin 47/6396 16/3327 1.53 (0.872.69)
Dapagliflozin 73/5936 62/3403 0.67 (0.480.94)
Empagliflozin 50/4687 60/2333 1.24 (0.931.67)
Empagliflozin 490/4687 282/2333 0.86 (0.750.99)
(I2=0%) 1.30 (1.001.68)
Ipragliflozin 7/628 10/368 0.41 (0.161.07) Unstable angina
(12 =43%) 0.84 (0.750.95) Canagliflozin 26/6396 18/3327 0.75 (0.411.37)

MACE plus Empagliflozin 133/4687 66/2333 1.00 (0.751.34)

(I2=0%) 0.95 (0.731.23)
Canagliflozin 130/6395 71/3327 0.95 (0.721.27)
Heart failure*
Dapagliflozin 97/5936 81/3403 0.69 (0.510.95)
Empagliflozin 126/4687 95/2333 0.65 (0.500.85)
Empagliflozin 621/7082 359/3547 0.87 (0.770.98) (I2=0%) 0.65 (0.500.85)
(12 =24%) 0.85 (0.770.95) All-cause death
Cardiovascular death Canagliflozin 49/6177 37/3262 0.70 (0.461.07)
Dapagliflozin 37/5936 24/3403 0.88 (0.531.48)
Canagliflozin 21/6396 16/3327 0.68 (0.361.31)
Empagliflozin 278/7082 201/3647 0.69 (0.580.82)
Empagliflozin 172/4687 137/2333 0.62 (0.500.78)
(I2=0%) 0.71 (0.610.83)
(12 =0%) 0.63 (0.510.77)
Non-fatal MI
Canagliflozn 45/6396 27/3327 0.87 (0.541.39)
Empagliflozin 213/4687 121/2333 0.88 (0701.09)
(12 =0%) 0.88 (0.721.07)

0.5 1.0 1.5 2.0 2.5 0.5 1.0 1.5 2.0 2.5
Relative risk Relative risk
Favours SGLT2 inhibitor Favours control Favours SGLT2 inhibitor Favours control

CI, confidence interval; MACE, major adverse cardiovascular event; MI, myocardial infarction; SGLT2, sodiumglucose co-transporter 2
Wu JH, et al. Lancet Diabetes Endocrinol 2016;4:4119
FORXIGA:
CV safety profile in a variety of patients
In a subgroup analysis of patients grouped by their degree of CV risk, FORXIGA
demonstrated a CV safety profile in patients with:1
Various degrees of CV risk
Established CVD
Differing numbers of prior CVD events

Cardiac failure: Experience in NYHA Class III is limited, and there is no experience in clinical studies with
FORXIGA in NYHA Class IIIIV.
FORXIGA is not recommended for use in patients receiving loop diuretics or who are volume depleted, e.g. due to
acute illness (such as gastrointestinal illness).
Caution should be exercised in patients for whom a dapagliflozin-induced drop in blood pressure could pose a risk,
such as patients with known CVD, patients on antihypertensive therapy with a history of hypotension or elderly
patients.
CV, cardiovascular; CVD, cardiovascular disease; NYHA, New York Heart Association; SBP, systolic blood
pressure.
1. Sonesson C, et al. Poster presented at the Annual Meeting of the European Society of Cardiology, Barcelona, Spain. 30 August3 September
2014. Poster 6094;
Clinical considerations when prescribing FORXIGA

FORXIGA is not recommended in:

Patients aged 75 years
Patients receiving loop diuretics
FORXIGA is also not recommended for initiation of therapy in patients who are volume
depleted
Temporary interruption of FORXIGA is recommended for patients who develop
volume depletion until the depletion is corrected
Caution should be exercised in patients for whom a FORXIGA-induced drop
in blood pressure could pose a risk
A lower dose an insulin secretagogue may be required to reduce the risk of
hypoglycaemia when used in combination with FORXIGA

FORXIGA. Summary of product characteristics, 2015.

FORXIGA:
Easy to initiate and manage

FORXIGA: Once-daily tablet1

Can be taken any time of the day,
regardless of meals1

No dose titration for the majority of

patients
ONE PILL
taken In patients with severe hepatic impairment, 10 mg
ONCE A DAY a starting dose of 5 mg is recommended, if
well tolerated, the dose may be increased
to 10 mg.1
No dosage adjustment is necessary for
patients with mild or moderate hepatic
impairment*1

FORXIGA pill are not shown at actual size.

*There is limited experience in clinical trials in patients with hepatic impairment.
FORXIGA exposure is increased in patients with severe hepatic impairment.
1. FORXIGA. Summary of product characteristics, 2016
Current Treatment

+ DPP4 inhibitor
Modest HbA1c reductions2
Metformin Weight neutral2
Low risk of hypoglycaemia2 FORXIGA
HbA1c reductions35
Weight loss35
First line Second line
SBP reductions*35
Insulin-independent
MoA6
Low risk of
+ Sulphonylurea
HbA1c reduction 8 hypoglycaemia4
Metformin Moderate risk of hypoglycaemia 7
Weight gain

First line Second line

The choice of diabetes therapies must be individualised based on attributes specific to both patients and the medications themselves.
*FORXIGA are not indicated for the management of weight loss or high blood pressure. Weight change was a secondary endpoint, and blood pressure
change was primarily assessed as a safety or exploratory efficacy endpoint in clinical trials.
The risk of hypoglycaemia is dependent on the type of background therapy used

DPP4, dipeptidyl peptidase-4; MoA, mechanism of action; SBP, systolic blood pressure; XR, extended release.
1. Garber AJ, et al. Endocr Pract 2016;22; 84113. 2. Inzucchi SE, et al. Diabetes Care 2015;38:1409. 3. Bailey CJ, et al. Lancet 2010;37:222333; 4. Bailey CJ, et al.
BMC Med 2013;11:43; 5. Del Prato S, et al. Diabetes Obes Metab 2015;17:58190; 6. FORXIGA. Summary of product characteristics, 2015. 7. Yehuda Handelsman, et
al. AACE/ACE Diabetes Guidelines, Endocr Pract. 2015;21(Suppl 1) 8. Diana Sherifali, et al. Diabetes Care 33:18591864, 2010
Consider FORXIGA as first add-on to metformin1

+ FORXIGA
HbA1c reductions35
Weight loss35
Metformin SBP reductions*35
Insulin-independent MoA6
Low risk of hypoglycaemia4

First line Second line Delivering

multiple benefits
earlier with FORXIGA
+ FORXIGA
HbA1c reductions35
Weight loss35
Metformin SBP reductions*35
Insulin-independent MoA6
Low risk of hypoglycaemia4

First line Second line

The choice of diabetes therapies must be individualised based on attributes specific to both patients and the medications themselves.
*FORXIGA are not indicated for the management of weight loss or high blood pressure. Weight change was a secondary endpoint, and blood pressure change
was primarily assessed as a safety or exploratory efficacy endpoint in clinical trials.
The risk of hypoglycaemia is dependent on the type of background therapy used

DPP4, dipeptidyl peptidase-4; MoA, mechanism of action; SBP, systolic blood pressure; XR, extended release.
1. Garber AJ, et al. Endocr Pract 2016;22; 84113. 2. Inzucchi SE, et al. Diabetes Care 2015;38:1409. 3. Bailey CJ, et al. Lancet 2010;37:222333; 4. Bailey CJ, et al. BMC
Med 2013;11:43; 5. Del Prato S, et al. Diabetes Obes Metab 2015;17:58190; 6. FORXIGA. Summary of product characteristics, 2015. 7. Yehuda Handelsman, et al.
AACE/ACE Diabetes Guidelines, Endocr Pract. 2015;21(Suppl 1) 8. Diana Sherifali, et al. Diabetes Care 33:18591864, 2010
Summary
FORXIGA
Has insulin-independent pathway, by removing excess glucose and calories
with urine4
Provide a significant reduction in PPG, FPG, HbA1C and sustained when
used as add-on to metformin, sulfonylureas and TZDs1,5
FORXIGA Provide added benefit of significantly reduce total body weight,
blood pressure1, waist circumference and body fat mass compared to
placebo when used as add-on therapy1,2
Significant and sustained weight loss and blood pressure1
FORXIGA well tolerated1,3

FORXIGA is not indicated for the management of obesity or high blood pressure. 1 Weight change was a secondary endpoint in clinical trials.1,5
*This information is an estimate derived from the use of information under licence from the following IMS Health information service: NPA Market Dynamics for period February April
2014. IMS expressly reserves the rights of copying, distribution and republication.
1. FORXIGA. Summary of product characteristics, 2014; 2. Del Prato S, et al. Presented at the 73rd American Diabetes Association Scientific Sessions, Chicago, USA. 2125 June
2013.
Abstract 62-LB; 3. Data on file (Cegedim Strategic Data, Longitudinal Patient Databases, October 2014); 4. Marsenic O. Am J Kidney Dis 2009;53:87583; 5. Bailey CJ, et al. Lancet
2010;375:222333.
FORXIGA:
For your patients who are uncontrolled on metformin

FORXIGA as add on to
metformin delivers significant
and sustained reductions in:1,2
PPG, FPG & HbA1c,
Wth ADDITIONAL Benefit
Reduction1 :
Weight
Blood pressure
Waist Circumference

Early disease Advanced disease

FORXIGA is not indicated for the management of obesity or high blood pressure.1 Weight change was a secondary endpoint in clinical trials.1,2
1. FORXIGA. Summary of product characteristics, 2014; 2. Bailey CJ, et al. Lancet 2010;375:222333; 3. Jabbour SA, et al. Diabetes Care 2014;37:74050;
6