Effect of hypoglycemic agents on ischemic preconditioning in patients with type 2 diabetes and symptomatic coronary artery disease

Diabetes Care. 2013 Jun;36(6):1654-9. doi: 10.2337/dc12-1495. Epub 2012 Dec 18.

Abstract

Objective: To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD).

Research design and methods: We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4).

Results: In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069).

Conclusions: Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Aged
  • Carbamates / adverse effects
  • Carbamates / therapeutic use
  • Coronary Artery Disease / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Ischemic Preconditioning*
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use
  • Piperidines / adverse effects
  • Piperidines / therapeutic use
  • Prospective Studies
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use
  • Vildagliptin

Substances

  • Carbamates
  • Hypoglycemic Agents
  • Nitriles
  • Piperidines
  • Pyrrolidines
  • repaglinide
  • Vildagliptin
  • Adamantane

Associated data

  • ISRCTN/ISRCTN62282580