Metformin Use May Moderate the Effect of DPP-4 Inhibitors on Cardiovascular Outcomes.

OBJECTIVE: To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH DESIGN AND METHODS: We performed a meta-analysis of the three major cardiovascular outcomes trials examining DPP-4i. We used meta-regression to examine how the cardiovascular effects of DPP-4i differ between prevalent metformin users and baseline nonusers. RESULTS: While prevalent metformin users experienced a trend toward improved cardiovascular outcomes with DPP-4i (summary hazard ratio [HR] 0.92 [95% CI 0.84, 1.01]), baseline metformin nonusers showed a trend toward harm (HR 1.10 [95% CI 0.97, 1.26]). The difference in overall DPP-4i effect between metformin user and nonuser subgroups was statistically significant (P = 0.036). CONCLUSIONS: Baseline metformin status may have a moderating effect on cardiovascular outcomes with DPP-4i use. This hypothesis-generating analysis suggests there is residual uncertainty as to how DPP-4i affect cardiovascular outcomes, depending on concurrently prescribed medications.

Duke Scholars

Author Matthew Janik Crowley Medicine, Endocrinology, Metabolism, and Nutrition

Author John Wiley Williams Jr. Medicine, General Internal Medicine

Author Andrzej Stanislaw Kosinski Biostatistics & Bioinformatics, Division of Biostatistics

Author David A D'Alessio Medicine, Endocrinology, Metabolism, and Nutrition