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Insulin Secretagogues: Sulfonylureas and “ Glinides ”

Insulin Secretagogues: Sulfonylureas and “ Glinides ”. Safety and Efficacy -Decreases HbA 1c approx 1–2%(sfu, repaglinide)(0.5-1.0%,neteglanide) -Adverse events: Wt gain, sulfa allergy (sfu,rare),  -cell apoptosis (sfu)

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Insulin Secretagogues: Sulfonylureas and “ Glinides ”

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  1. Insulin Secretagogues: Sulfonylureas and “Glinides” • Safety and Efficacy -Decreases HbA1c approx1–2%(sfu, repaglinide)(0.5-1.0%,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.

  2. 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):753-759.

  3. Increased Mortality with SU Endo 2012, abstract Fits FDA criteria for market withdrawal DOI: 10.1177/1479164112465442 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. 2012 Nov 6;110(9 Suppl):13B-23B

  4. 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

  5. Glycemic Benefit of Ranolazine: Proportional to Baseline HgA1c

  6. MERLIN TIMI-36 Safety of Ranexa in PatientsWith Diabetes *p for interaction = 0.29.†p for interaction = 0.68. Morrow DA, et al. Circulation. 2009;119:2032-2039.

  7. 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

  8. 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

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