Potential Positive Interactions Between DPP-4 Inhibitors and Metformin in Cardiovascular Cases

Patients with diabetes may benefit, but clinical impact not clear

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Cardiovascular (CV) outcomes appeared more favorable when dipeptidyl peptidase-4 (DPP-4) inhibitors were initiated in patients using metformin, according to two recent diabetes-focused studies. These findings suggest that DPP-4 inhibitors and metformin may interact to determine CV outcomes in type 2 diabetes.

Authors of a November 2018 study published in Diabetes, Obesity & Metabolism, a follow-up to a 2017 Diabetes Care meta-analysis, say that these results are potentially significant. Matthew J. Crowley, MD, MHS, a Duke diabetes researcher and lead author of both studies, emphasized that these findings could change researchers’ approach to DPP-4 inhibitors and other diabetes medications.

“While DPP-4 inhibitors are widely held to have neutral CV effects, our studies suggest that their effects may actually vary based on co-prescribed medications. In both studies, outcomes were better when DPP-4 inhibitors were initiated with baseline metformin use than when they were initiated without baseline metformin, which suggests a possible interaction between the two agents.”

In both studies, the authors determined that baseline patient metformin status may have a moderating effect on CV outcomes with the use of DPP-4 inhibitors. However, Crowley emphasized that further clinical studies are needed to explore ways in which interactions between glucose-lowering medications might affect clinical outcomes in diabetes. He remained cautious about recommending that clinicians change prescribing at this time.

“While we’re excited about these findings, the clinical implications are not yet clear,” Crowley says. “More research is needed to address some of the limitations to the work we’ve done and to more comprehensively understand how glucose lowering medications interact. As a result, I don’t think that clinicians should change the way they prescribe DPP-4 inhibitors or other diabetes medications at this time. But we remain engaged in additional research that will further explore this area and should lead to some interesting conclusions.”

DPP-4 inhibitors are not considered initial therapy for the majority of patients with type 2 diabetes, but may be recommended for patients who are intolerant of, or have contraindications to, metformin, sulfonylureas, or thiazolidinediones. These patients are typically those with chronic kidney disease or those at high risk for hypoglycemia.