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Metformin and Cardiovascular Risk

Jan 28, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Antonio Bess, Pharm D Candidate, Florida Agricultural & Mechanical University School of Pharmacy

New analysis continues to build the case for metformin and cardiovascular benefits.

Metformin has been recommended as first-line therapy for type 2 diabetes mellitus (T2DM) by the American Diabetes Association and European Association for the Study of Diabetes. Although metformin has proven benefits in reducing plasma glucose levels and reducing microvascular complications, its effect on cardiovascular complications in patients with T2DM is less clear.  One meta-analysis found that following treatment with metformin, there were reduced cardiovascular mortality, all-cause mortality, and cardiovascular events in patients with coronary artery disease. Newer studies are being conducted that are comparing dual anti-glycemic regimens vs. metformin monotherapy. Therefore, if metformin can prove to have cardiovascular benefits, its use will be further supported.


This meta-analysis was conducted by searching Pubmed, Embase, and CNKI (China National Knowledge Infrastructure) databases for articles published between 1980 to 2019 on the association of cardiovascular risk following metformin treatment in patients with type 2 diabetes mellitus. Metformin users were compared to non-users with T2DM. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the case-control and cohort studies. The inclusion criteria for each study was the following: 1. evaluate the association of cardiovascular risk following metformin treatment in patients with T2DM; 2. inclusion of sufficient data or the data can be acquired from the manuscript or supplementary materials to calculate ORs and 95% CIs; 3. the publication was a cohort study; 4. the study was published in English. The studies had high levels of heterogeneity between them (I^2 = 96.5% for mortality, and I^2 = 98.5% for incidence). There were no factors that could influence initial heterogeneity.

In total, 16 studies were included, and 25 comparisons met the inclusion criteria. Total participants included 1,160,254 patients with T2DM and 708,843 patients with T2DM who were taking metformin. The study results found statistical evidence of significantly decreased cardiovascular risk to be associated with metformin treated patients (OR = 0.57, 95% CI = 0.48-0.68), both with the mortality (OR = 0.44, 95% CI = 0.34-0.57) and incidence (OR = 0.73, 95% CI = 0.59-0.90). In the sub-group analysis, metformin proved to have a significantly decreased cardiovascular risk when compared to sulfonylureas (OR = 0.50, 95% CI = 0.38-0.64), both with the mortality (OR = 0.34, 95% CI = 0.17-0.67) and incidence (OR = 0.70, 95% CI = 0.55-0.89).

This study indicates that treatment with metformin in a person with T2DM is associated with decreased cardiovascular risk, both with the mortality and incidence, and that metformin is more effective than sulfonylureas in reducing risk. Limitations of the study were possible bias, and only studies that reported OR’s and 95% CI’s were included. The large population and time support the results of this study. Future studies can focus on subgroup analysis on which community receives the most significant benefit from metformin.

Practice Pearls:

  • Metformin reduces cardiovascular risk in patients with T2DM.
  • Metformin is more significant lowering cardiovascular risk compared to sulfonylureas.
  • Adequate glucose control is beneficial to micro and macrovascular complications.

 Zhang, Kui, et al. “Cardiovascular Risk Following Metformin Treatment in Patients with Type 2 Diabetes Mellitus: Results from Meta-Analysis.” Diabetes Research and Clinical Practice, vol. 160, Elsevier Ireland Ltd, Feb. 2020, doi:10.1016/j.diabetes.2020.108001.

Antonio Bess, Pharm D Candidate, Florida A&M University


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