Metformin May Improve Clinical Outcomes in Comorbid Heart Failure and Diabetes

Researchers assessed the clinical outcomes of patients with comorbid heart failure and diabetes receiving treatment with metformin and sulfonylurea.

Metformin is associated with improved clinical outcomes among adults with comorbid diabetes and heart failure (HF), particularly patients with ejection fraction (EF) greater than 40%, according to a study published in JACC: Heart Failure.

For the observational study, researchers used data on 5852 Medicare beneficiaries with diabetes admitted to 367 US hospitals for HF from 2006 to 2014. Among them, 7.8% were prescribed metformin for the first time, and 8.6% were newly prescribed sulfonylurea. Parallel analyses were performed in which individuals with newly prescribed metformin and sulfonylurea were separately compared with those not given therapy. Multivariable models evaluating relationships between therapy prescription and 12-month HF mortality and hospitalization were landmarked at 90 days postdischarge. Influenza vaccination and hospitalization for urinary tract infection or gastrointestinal bleed constituted falsification endpoints. Subgroups were categorized by EF less than or equal to 40% vs greater than 40%.

An independent association was identified between metformin prescription and lower risk for composite death and hospitalization for HF (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98; P =.03), though individual associations were not statistically significant (metformin initiation and all-cause death, P =.59; metformin initiation and HF hospitalization, P =.072). The subgroup with EF greater than 40% was at lower risk for HF hospitalization (HR, 0.58; 95% CI, 0.40-0.85; P =.007) and the composite endpoint (HR, 0.68; 95% CI, 0.52-0.90; P =.040), while risk was not reduced for those with EF less than or equal to 40%.

Adjusting for covariates revealed an association between sulfonylurea and increased risk for death (HR, 1.24; 95% CI, 1.00-1.52; P =.045) and hospitalization for HF (HR, 1.22; 95% CI, 1.00-1.48; P =.050). These associations persisted regardless of EF. No association was identified between either therapy and falsification endpoints.

Limitations to this study include an observational design and inability to determine causality, an inability to assess adherence postdischarge, a limited sample size, incomplete covariate data, the exclusion of those with severe chronic kidney disease, and a potential lack of generalizability due to the inclusion of only Medicare beneficiaries aged 65 years and older.

“In this US cohort of older patients hospitalized for HF with [diabetes], initiation of metformin therapy was associated with decreased 12-month mortality and HF hospitalization, driven by substantial associated benefits among patients with EF [greater than]40%,” the study authors noted. “By contrast, sulfonylurea prescription was associated with excess risk of mortality and HF hospitalization regardless of EF.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Khan MS, Solomon N, DeVore AD, et al. Clinical outcomes with metformin and sulfonylurea therapies among patients with heart failure and diabetes. J Am Coll Cardiol HF. Published online December 8, 2021. doi: 10.1016/j.jchf.2021.11.001