An initiative of South Asian Federation of Endocrine Societies (SAFES)
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Transcript of An initiative of South Asian Federation of Endocrine Societies (SAFES)
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