Matthew J Crowley1,2, John W Williams3,4, Andrzej S Kosinski5, David A D'Alessio2, John B Buse6. 1. Durham Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, NC matthew.crowley@dm.duke.edu. 2. Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, NC. 3. Durham Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, NC. 4. Division of General Internal Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC. 5. Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, NC. 6. Division of Endocrinology & Metabolism, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
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.
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.
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