Dpp4 inhibition as a therapeutic strategy in cardiometabolic disease: Incretin-dependent and -independent function

• Discuss the findings from recent large scale clinical trials (EXAMINE and SAVOR-TIMI 53)
• Summarize the catalytic dependent and independent effects of DPP4 inhibition on cardiometabolic disease
• Focus on recent evidence linking DPP4 inhibition therapy with cardiovascular disease
• Provide mechanistic insights into the cardiovascular effect of DPP4

Cardiometabolic disorders including obesity, diabetes and cardiovascular disease are among the most severe health problems worldwide. DPP4 enzymatic inhibitors were first developed as anti-diabetic reagents which preserve incretin hormones and promote post-prandial insulin secretion. It's been shown in animal studies that incretin-based therapy has a beneficial effect on cardiovascular disease. Recent studies demonstrated novel non-catalytic functions of DPP4 that may play a role in cardiometabolic disease. Although the role of DPP4 inhibition-mediated incretin effects has been well-reviewed, little information of its incretin-independent actions was introduced in cardiometabolic disease. In the current review, we will summarize the catalytic dependent and independent effects of DPP4 inhibition on cardiometabolic disease.