1. Insulin Secretagogues: Sulfonylureas and “Glinides”
Safety and Efficacy
-Decreases HbA1c approx 1–2%(sfu, repaglinide)( %,neteglanide)
-Adverse events:
Wt gain,
sulfa allergy (sfu,rare),
-cell apoptosis (sfu)
Main risk = hypoglycemia , inc ischemia risk(~50% less w/repaglinide,75% less with neteglanide)
Increase Cancer vs Metformin
Abnormal ischemia pre-conditioning
SO WHY USE SOMETHING THAT DESTROYS BETA-CELLS - and you’ll need more expensive agents ANYWAY, in 3 years when SU stops working
Davies MJ. Curr Med Res Opin. 2002;18(Suppl 1):s22-30. 1

3. CV Risk of SU and Insulin
So benefit of both SU/Insulin in
research studies –UKPDS, DCCT/EDIC
But adverse risk in ‘real world’ use
Pharmacoepidemiology and Drug Safety. 2008;(17):

4. Increased Mortality with SU
Endo 2012, abstract
Fits FDA criteria for
market withdrawal
DOI: /
Diabetes and Vascular Disease Research published online 4 January 2013
Thomas Forst, Markolf Hanefeld, Stephan Jacob, Guido Moeser, Gero Schwenk, Andreas Pfützner and Axel Haupt
review and meta-analysis of observational studies
Acute coronary syndrome in patients with diabetes mellitus: perspectives of an interventional cardiologist.
Sanon S, Patel R, Eshelbrenner C, Sanon VP, Alhaddad M, Oliveros R, Pham SV, Chilton R.
Am J Cardiol Nov 6;110(9 Suppl):13B-23B

5. Other Meds with ‘synergistic’ Glycemic and CV Benefit
Alpha-glucosidase Inhibitors
Acarbose – CV outcome benefit in pre-diabetes!!
Colsevelam
lipid benefit
(Ranolazine)
Decrease angina ( or equivalent)
Decreases arrhythmia
Improves diastolic dysfunction, thus-decreases edema of Pio-,
Decreases HgA1c, FBS in glucose dependent fashion , no hypoglycemia

6. Glycemic Benefit of Ranolazine: Proportional to Baseline HgA1c

7. Safety of Ranexa in Patients With Diabetes
MERLIN TIMI-36
Safety of Ranexa in Patients With Diabetes HR
95% CI
p Value*
Recurrent ischemia
Overall cohort vs placebo
0.87
0.76–0.99
0.03
Patients with diabetes vs placebo
0.75
0.61–0.93
0.008*
Patients with diabetes vs without diabetes
0.95
0.80–1.11
0.10
Death, any cause
0.98
0.70–1.36
0.91
CV death or MI
1.09
0.86–1.38
0.46*
New or worsening heart failure
1.01
0.73–1.39
0.95†
Sudden cardiac death
0.76
0.41–1.39
0.37
*p for interaction = †p for interaction = 0.68.
Morrow DA, et al. Circulation. 2009;119:

8. RANEXA CAN BE USED IN PATIENTS WITH CAD AND DIABETES
Ranexa does not increase the incidence of hypoglycemia compared with placebo
Ranexa does not increase
the incidence of:
Weight gain
Cardiovascular adverse events
Dyslipidemia (LDL, HDL, total cholesterol,
and triglycerides)
Clinically relevant changes in
blood pressure or heart rate
Timmis AD, et al. Eur Heart J 2006;27:42-48

9. Ranolazine may be VERY Beneficial in Patients With Diabetes
1. avoid hypoglycemic agents- use Metformin/Incretin/tzd//bromocryptine/ ranolazine for CV/ glucose
2. In patients with TZD edema, diastolic dysfunction benefit obviates Edema
3. Ranolazine / Incretins peri-op / peri-cath for cardio-protection
4. ?incretin/ranolazine similarities- heart/beta cell-
? no additional benefit, additive, supra-additive