DPP-inhibitors reduce cardiovascular events in diabetes patients

By Andrew Czyzewski, medwireNews Reporter

Type 2 diabetes patients who are treated with dipeptidyl peptidase-4 inhibitors (DPP4i) have a significantly reduced risk for cardiovascular events, particularly myocardial infarction (MI), compared with their peers who take placebo or other drugs, results of a meta-analysis show.

The findings corroborate previous studies, and additional data suggest that DPP4i go beyond simply modifying risk factors through glycemic control and may have additional actions of cardiovascular protection.

Nevertheless, Edoardo Mannucci (University Hospital Careggi, Florence, Italy) and colleagues caution that previous DPP4i trials were primarily designed to assess the drugs' efficacy on glycemic control and their tolerability and safety.

"The analysis supports the safety of DPP4i but it does not demonstrate their efficacy in reducing cardiovascular risk on a long-term basis. For this latter issue, we should await the results of the ongoing trials with cardiovascular events as the major endpoint," the researchers comment in the journal Diabetes, Obesity and Metabolism.

Mannucci and colleagues reviewed 70 trials including a total of 41,959 patients with Type 2 diabetes who were assigned to one of two arms: DPP4i treatment or placebo or other drugs.

After an average follow up of 44.1 weeks across the studies, patients treated with DPP4i were found to have better outcomes than their peers, including a reduced incidence of major cardiovascular events (MACE), MI, stroke, and mortality, with Mantel-Haenzel odds ratios of 0.71, 0.64, 0.77, and 0.60, respectively.

Discussing the findings, the researchers note that this reduction of MACE after a relatively short-term treatment is "unexpected" because drugs that are known to modify risk factors usually require a much longer treatment to produce detectable results on cardiovascular events.

This would suggest that DPP4i, besides improving glucose control and producing the small beneficial effects on lipid profile and blood pressure, have additional actions.

"Several mechanisms possibly lead to cardiovascular protection by DPP4i. These include GLP-1-induced myocardial protection and enhancement of endothelial function, increased endothelial progenitor cell availability and other GLP-1 independent endothelial effects," Mannucci and colleagues comment.

The findings are published in the journal in Diabetes, Obesity and Metabolism.

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