SGLT-2 inhibitors associated with reduced heart failure events versus metformin

Patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitors as a first-line type 2 diabetes treatment had a lower risk for hospitalization or death from heart failure compared to those on metformin, a study found.

Researchers conducted a population-based cohort study of claims data from two large U.S. commercial and Medicare databases from April 2013 to March 2020. Results were published May 24 by Annals of Internal Medicine.

Among 8,613 patients on SGLT-2 inhibitors matched to 17,226 metformin patients, there was a similar risk for a composite outcome of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (hazard ratio [HR], 0.96; 95% CI, 0.77 to 1.19). However, on a composite of hospitalization for heart failure or all-cause mortality, SGLT-2 inhibitor patients had a lower risk (HR, 0.80; 95% CI, 0.66 to 0.97) during a mean follow-up of 12 months.

Patients taking SGLT-2 inhibitors showed a lower risk for heart failure hospitalization (HR, 0.78; 95% CI, 0.63 to 0.97) and a numerically lower risk for MI (HR, 0.70; 95% CI, 0.48 to 1.00) than those on metformin. Patients taking SGLT-2 inhibitors had a higher risk for genital infections (HR, 2.19; 95% CI, 1.91 to 2.51), but otherwise the drugs showed similar safety profiles.

The authors cautioned that their results were limited by the nonrandomized design, but they noted that across all cardiovascular outcome trials, SGLT-2 inhibitors showed a 27% to 35% reduction in the risk for heart failure hospitalization relative to placebo, implying a class effect through hemodynamic pathways. They concluded that the results may support the use of SGLT-2 inhibitors as a first-line therapy, but that a randomized clinical trial is warranted to establish more robust evidence.