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

• Published in: Diabetes care Vol. 40; no. 12; pp. 1787 - 1789
• Main Authors: Crowley, Matthew J, Williams, Jr, John W, Kosinski, Andrzej S, D'Alessio, David A, Buse, John B
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.12.2017
• Subjects: Antidiabetics; Cardiovascular disease; Clinical outcomes; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Drug Interactions; Drug therapy; Humans; Inhibitor drugs; Inhibitors; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Peptidase; Proportional Hazards Models; Regression analysis; Research design; Statistical analysis; Subgroups; Treatment Outcome
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc17-1528

To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i). 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. 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 ( = 0.036). 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.