an initiative of south asian federation of endocrine societies (safes)
DESCRIPTION
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:TRANSCRIPT
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