1. An initiative of South Asian Federation of Endocrine Societies (SAFES)

2. SAFES Consensus Statement Endorsement Glimepiride Gliclazide MR Indian J Endocr Metab 2015;19:577-96. Modern SUs

3. SAFES Consensus Statement Endorsement Modern SUs should be preferred over conventional SUs in view of Reduced mortality Better CV outcomes Renal protection Indian J Endocr Metab 2015;19:577-96.

4. SAFES Recommendation Modern SUs should be preferred over conventional SUs in view of the reduced mortality, better CV outcomes, and renal protection. Indian J Endocr Metab 2015;19:577-96.

5. Monami M, et al. Diabetes Metab Res Rev 2006; 22(6): 477-482 Kaplan-Meier survival analysis Glimepiride or gliclazide Repaglinide Glibenclamide Time (months) Cumulative survival 1.0 0.9 0.8 0.7 0.6 010.020.030.040.0 Glimepiride Gliclazide Repaglinide Glibenclamide Yearly mortality 0.4% 2.1%* 3.1%* 8.7%** * P < 0.05 vs Glimepiride **P <0.01 vs all comparators Evidence on Mortality with Modern SUs Glimepiride & Gliclazide are associated with lower all-cause mortality than other SUs

6. J Clin Endocrinol Metab. 2010 Nov;95(11):4993-5002 Evidence on CV safety with Modern SUs Glimepiride & Gliclazide have lower CV risk than older SUs

7. Meta-analysis comparing a SU vs a non-SU agent in T2DM End points: Major cardiovascular events (MACE) and mortality An overall OR for MACE with SU treatment vs comparators was 1.08 thus detecting no signal for cardiovascular risk Use of SU was not associated with any significant difference in the incidence of MI with respect to comparators (OR: 0.88) Diabetes Obes Metab. 2013 Oct;15(10):938-53 Evidence on CV safety: SUs vs other AHA

8. JAMA. 2014 Jun 11;311(22):2288-96. SU vs Insulin as add on to metformin: Reduced Cardiovascular Events and Mortality Evidence on CV safety: SUs vs Insulin

9. SAFES Recommendation Modern SUs should be preferred over conventional SUs in view of the reduced mortality, better CV outcomes, and renal protection. Modern SUs should be preferred over conventional SUs in T2DM patients at increased risk of hypoglycemia. Indian J Endocr Metab 2015;19:577-96.

10. Incidence of severe* hypoglycemic events according to treatment *Defined as requiring IV glucose or glucagon Significantly lower incidence of severe hypoglycemic events with Glimepiride Holstein A et al. Diabetes Met Res Rev 2001; 17:467-73 0.86 5.6 GlibenclamideGlimepiride # Episodes/1000 person- years 0 2 4 6 Hypoglycemia Incidence: Modern vs Older SUs

12. SAFES Recommendation Modern SUs should be preferred over conventional SUs in view of the reduced mortality, better CV outcomes, and renal protection. Modern SUs should be preferred over conventional SUs in T2DM patients at increased risk of hypoglycemia. Modern SUs should be the preferred choice of SU in overweight/obese T2DM patients. Indian J Endocr Metab 2015;19:577-96.

13. Modern SUs are Weight Neutral Changes in bodyweight [in relation to body mass index (BMI) at baseline in patients with T2DM during therapy with glimepiride Clin Drug Invest 2001; 21 (9): 597-604 Glimepiride was associated with weight neutrality/Weight loss in patients with greater BMI

14. Clinical differences between Glimepiride and Gliclazide MR Outcomes Microvascular and Macrovascular

15. N Engl J Med. 2015 Jun 4;372(23):2197-206 N Engl J Med 2008;358:2560-72 Recent Clinical Outcome Trials: Intensive vs Standard therapy VADT/FS: Glimepiride used in the intensive arm along with other OADs and insulin ADVANCE: Gliclazide MR used in Intensive arm along with 40% insulin, other OHA: 93% VADT – FS: Veteran's Affairs Diabetes Trial - Follow-up Study ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation

16. N Engl J Med. 2015 Jun 4;372(23):2197-206 Glimepiride used in intensive arm along with other OADs and insulin 17% RRR in CV events, effect on Microvascular complications were not studied HbA1c reached: 6.9% in intensive arm vs 8.4% in standard therapy arm VADT/FS: Clinical Outcome Results

17. Intensive vs Standard therapy: Effect on primary outcome of the time to the first major cardiovascular event N Engl J Med. 2015 Jun 4;372(23):2197-206 The intensive-therapy group (having glimepiride) had a significant 17% RRR in major CV events 2015 VADT/FS: Clinical Outcome Results

18. N Engl J Med 2008;358:2560-72 ADVANCE: Gliclazide MR used in Intensive arm along with 40% insulin, other OHA: 93% HbA1c reached: 6.5% in intensive arm vs 7.3% in the standard therapy arm 10% RRR in combined Micro- and Macrovascular events  Due to a 16% RRR reduction in Microvascular events (nephropathy) No effect seen on Major Macrovascular events ADVANCE: Clinical Outcome Results

19. ADVANCE study: No effect on CVD outcomes N Engl J Med 2008;358:2560-72 Benefit driven by reduction in Nephropathy due to better control of HbA1c

20. Thank You