Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease

Abstract

OBJECTIVETo assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD).RESEARCH DESIGN AND METHODSWe 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).RESULTSIn 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).CONCLUSIONSRepaglinide 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.

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…Hueb et al (2007) demonstrated in diabetic patients that treatment with repaglinide (a K ATP channel antagonist) blocked the ischemic preconditioning effect against exercise-induced myocardial ischemia. Using a similar clinical model, Rahmi et al (2013) confirmed the negative effect of repaglinide on preconditioning but also found that vildagliptin did not block preconditioning's protection. The protection by remote ischemic preconditioning is abrogated in diabetic CABG patients when treated with sulphonylureas (Kottenberg et al, 2014b).…”

Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors: From Risk Factors to Clinical Outcomes

“…A large body of animal experiments now provides compelling evidence for the advantageous impact of DPP-4 inhibition in the ischemia/reperfusion injury model 102 . Human data showed that vildagliptin does not damage the protective mechanism of myocardial ischemic preconditioning in patients with T2DM and coronary artery disease, in contrast to repaglinide, a glucoselowering agent acting as K(ATP) channel blocker (a mechanism shared by sulfonylureas) 103 .…”

Treatment of type 2 diabetes, lifestyle, GLP1 agonists and DPP4 inhibitors

“…DPP-4 inhibitors have been less well studied in cardiac ischaemic preconditioning. In a study by Rahmi et al [84] rapaglinide, a sulphonylurea like drug, inhibited ischaemic preconditioning as measured by stress testing in patients with type 2 diabetes who already had evidence of coronary atherosclerosis. Vildagliptin, a DPP-4 inhibitor, did not alter preconditioning in 72% of patients whereas 83% of the repaglinide patients had ischaemia earlier in their stress test.…”