Metformin Use May Moderate the Effect of DPP-4 Inhibitors on Cardiovascular Outcomes
Abstract
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.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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