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

Matthew J Crowley1,2, John W Williams3,4, Andrzej S Kosinski5

  • 1Durham Center for Health Services Research in Primary Care, Durham VA Medical Center, Durham, NC matthew.crowley@dm.duke.edu.

Diabetes Care
|October 21, 2017
PubMed
Abstract

Insights

Metformin use may alter cardiovascular outcomes for patients taking dipeptidyl peptidase 4 inhibitors (DPP-4i). This suggests DPP-4i effects on heart health may depend on concurrent medication, warranting further investigation.

Area of Science:

  • Cardiology
  • Pharmacology
  • Endocrinology

Background:

  • Dipeptidyl peptidase 4 inhibitors (DPP-4i) are widely used for type 2 diabetes.
  • Concerns exist regarding their cardiovascular safety.
  • Metformin is a common first-line antidiabetic medication.

Purpose of the Study:

  • To investigate whether metformin use modifies the cardiovascular effects of DPP-4 inhibitors.
  • To analyze cardiovascular outcomes in DPP-4 inhibitor trials based on prior metformin use.

Main Methods:

  • Meta-analysis of three major cardiovascular outcomes trials of DPP-4 inhibitors.
  • Meta-regression analysis to compare effects between prevalent metformin users and nonusers.

Main Results:

  • DPP-4 inhibitors showed a trend toward improved cardiovascular outcomes in prevalent metformin users (HR 0.92).
  • A trend toward harm was observed in baseline metformin nonusers (HR 1.10).
  • The difference in DPP-4 inhibitor effects between subgroups was statistically significant (P=0.036).

Conclusions:

  • Baseline metformin use may moderate cardiovascular outcomes associated with DPP-4 inhibitors.
  • Residual uncertainty exists regarding DPP-4 inhibitor cardiovascular effects based on concomitant medications.
  • Further research is needed to clarify these interactions.

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