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Do Incretin Medications Improve Cardiovascular Disease?

The effects of GLP-1 agonists and DPP-IV inhibitors on cardiovascular safety…. 

Because cardiovascular disease is a leading cause of morbidity and mortality in people with diabetes, managing and minimizing cardiovascular risk is a critical function in managing diabetes. Incretin based medications are relatively new medications to help treat type 2 diabetes. Glucagon-like peptide 1 (GLP-1) agonists and DPP-IV inhibitors are two classes of such drugs. GLP-1 agonists stimulate insulin release as well as inhibit glucagon release. DPP-IV inhibitors prevent GLP-1 agonists from being inactivated by DPP-IV and also decrease glucose. Previous studies have shown that GLP-1 agonists are associated with beneficial effects on cardiovascular risk factors. There have also been studies that show that incretin-based therapies have no increased risk of major adverse cardiovascular events. This particular study reviews randomized clinical trials to see what evidence there is for incretin-based therapies (GLP-1 agonists and DPP-IV inhibitors) and cardiovascular safety.

A literature search was performed and a total of 11 randomized clinical trials were used to identify long-term cardiovascular outcomes with incretin-based therapies in individuals with type 2 diabetes. From these studies the effects of GLP-1 and DPP-IV inhibitors were analyzed in cardiovascular risk factors. Factors like body weight, blood pressure, lipid profile, heart rate, QT interval, and cardioprotective effects were analyzed. When it comes to GLP-1 agonists, they are associated with weight loss, lower systolic blood pressure, lower LDL levels, non-elevated heart rate, and no significant QTc prolongation. There is also a possibility that GLP-1 agonists can provide a cardioprotective effect following myocardial infarction. Retrospective analyses show that GLP-1 agonist show no elevated risk of major adverse cardiovascular events. Prospective analyses are currently being done to confirm this.

DPP-IV inhibitors on the other hand have fewer studies done on their cardiovascular effects. They do not have major effects on weight, and there is limited evidence to suggest that it may reduce systolic blood pressure. It has negligible effects on fasting lipid levels as well as heart rate. DPP-IV inhibitors also do not contribute to QT prolongation in healthy individuals and show no risk of major adverse cardiovascular events in retrospective studies. Like GLP-1 agonists, current prospective analyses are being conducted to verify this.

In conclusion, incretin-based therapies not only have glucose lowering properties, but also beneficial effects on cardiovascular risk factors. There is also evidence that GLP-1 agonists have cardioprotective effects following a myocardial infarction. These studies show promise in their use in managing diabetes over other more established diabetic medications.

Practice Pearls:
  • Cardiovascular disease is a leading cause of morbidity and mortality in people with diabetes.
  • Incretin-based therapies have been shown to lower weight, blood pressure, lipid profiles, and heart rate with no effects on QT prolongation.
  • Long term cardiovascular outcomes are still being studied for incretin-based medications. 

Diabetes/Metabolism Research & Reviews 2014: Petrie, J. "The Cardiovascular Safety of Incretin-Based Therapies: A Review of the Evidence." Cardiovasc Diabetol. 2013;12(130)