A review on cardiovascular outcome studies of dipeptidyl peptidase-4 inhibitors

Abstract

The U.S. Food and Drug Administration issued a guidance for pharmaceutical industry defining preapproval and postapproval requirements for the demonstration of cardiovascular (CV) safety for all new medications developed for glycemic management in type 2 diabetes. However, results published from the studies of dipeptidyl peptidase-4 (DPP-4) inhibitors are conflicting with regard to different CV endpoints. Upcoming CV outcome studies perhaps will be able to provide additional insights related to diabetes management and help to provide the answers to some of these concerns. This article provides a brief overview regarding how various CV safety evidence of DPP-4 inhibitor evolved over time that highlights possible implication in clinical practice and translates them into effective diabetes management.

Impact of Dipeptidyl Peptidase-4 Inhibitors on Glycemic Control and Cardiovascular Safety with Adherence: An Overview

“…It was as- sociated with significantly improved glycemic control and reduced the development and progression of microalbuminuria. Another interesting finding was a higher number of hypoglycemic events in the saxagliptin group compared to the placebo group [16]. In a clinical trial SAVOR (Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus) a total of 16,492 patients were randomized.…”

“…Patients with T2DM have a two- to six-fold higher incidence of cardiovascular disease (CVD) than the nondiabetic population, making CVD as a leading cause of death in such patients. Therefore, the primary aim of glycemic control is focused on preventing death and morbidity due to CVD and microvascular diseases [16]. The earlier antidiabetic agents such as biguanides, sulfonylureas, and thiazolidinediones have not been tried for cardiovascular safety in large outcome trials.…”

“…The earlier antidiabetic agents such as biguanides, sulfonylureas, and thiazolidinediones have not been tried for cardiovascular safety in large outcome trials. Metformin showed a reduction in cardiovascular events when analyzed in an inadequately powered subgroup with a small number of patients in the UK Prospective Diabetes Study trial; thus, at present there is limited evidence to prove that existing antidiabetic agents are cardioprotective [16].…”

“…In addition, assessment of NT-pro-BNP concentration from baseline to 6 months did not reveal any significant changes. In the two groups of acute and chronic pancreatitis the incidence rates were similar [16].…”

“…The VIVIDD trial reported that diabetic patients with heart failure receiving vildagliptin showed no adverse effect on ejection fraction compared to patients receiving placebo. Though the primary endpoint indicated that vildagliptin did not have an unfavorable effect on LV ejection fraction, there was in fact an increase in LV end-diastolic volume ( p = 0.007) and a 14% decrease in brain natriuretic peptide in the vildagliptin group, suggesting that the increased LV volumes observed did not result in increased LV wall stress [16].…”