Is SGLT-2 inhibitor better than metformin as first-line T2D treatment?

Use of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) as first-line treatment for type 2 diabetes (T2D) delivers a comparable risk for myocardial infarction (MI), stroke, and mortality; a lower risk for hospitalization for heart failure (HHF)/mortality and HHF; and a similar safety profile, except for a higher risk for genital infections, when compared to treatment with metformin, a study has found.

Claims data were obtained from two large US commercial and Medicare by the investigators of this population-based cohort study. They identified T2D patients aged ≥18 years who initiated treatment with SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin during April 2013 to March 2020, without any use of antidiabetic medications prior to cohort entry.

Pooled hazard ratios (HRs) and 95 percent confidence intervals (CIs) were calculated after 1:2 propensity score matching in each database.

A total of 8,613 first-line SGLT-2i initiators were matched to 17,226 metformin users. Over a mean follow-up of 12 months, T2D patients treated with SGLT-2i had a similar risk for MI/stroke/mortality (HR, 0.96, 95 percent CI, 0.77‒1.19) and a lower risk for HHF/mortality (HR, 0.80, 95 percent CI, 0.66‒0.97) relative to metformin initiators.

The SGLT-2i group also had a reduced risk for HHF (HR, 0.78, 95 percent CI, 0.63‒0.97), a numerically lower risk for MI (HR, 0.70, 95 percent CI, 0.48‒1.00), and comparable risk for stroke, mortality, and MI/stroke/HHF/mortality compared with the metformin group.

Additionally, SGLT-2i initiators showed a higher risk for genital infections (HR, 2.19, 95 percent CI, 1.91‒2.51) but otherwise similar safety as those treated with metformin.

The study was limited by the nonrandomization of treatment selection.