An initiative of

South Asian Federation of Endocrine Societies (SAFES)

SAFES Consensus Statement Endorsement

• Glimepiride

• Gliclazide MR

Indian J Endocr Metab 2015;19:577-96.

Modern SUs

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.

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.

Monami M, et al. Diabetes Metab Res Rev 2006; 22(6): 477-482

Kaplan-Meier survival analysis

Glimepiride or gliclazide

Repaglinide

Glibenclamide

Time (months)

Cum

ulative survival

1.0

0.9

0.8

0.7

0.6

0 10.0 20.0 30.0 40.0

Glimepiride GliclazideRepaglinideGlibenclamide

Yearly mortality0.4%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

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

• 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

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

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.

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

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.

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

Clinical differences between Glimepiride and Gliclazide MR

Outcomes Microvascular and Macrovascular

N Engl J Med. 2015 Jun 4;372(23):2197-206N 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 StudyADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation

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

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

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

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

Thank You