Boston, MA—Clinical guidelines usually call for metformin as the preferred first-line treatment for type 2 diabetes (T2D), but a new study raises the question of whether that should be the case.

The study team from Brigham and Women's Hospital and Harvard Medical School pointed to the possibility of the use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2is).

The article in Annals of Internal Medicine advised that the evidence on the risk for cardiovascular (CV) events associated with the use of an SGLT-2i compared with metformin has been limited. That prompted researchers to assess CV outcomes among adults with T2D who initiated first-line treatment with an SGLT-2i instead of metformin.

The population-based cohort study used claims data from two large U.S. commercial and Medicare databases from April 2013 to March 2020. Participants were adults with T2D, including those aged 65 years and older on Medicare who began treatment with an SGLT-2i or metformin during that time period. The patients had not been prescribed any antidiabetic medications before cohort entry.

The focus was on the use of either a first-line SGLT-2i—anagliflozin, empagliflozin, or dapagliflozin—or metformin. The primary outcomes were defined as a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Researchers also tracked any genital infections reported in the group.

Results indicated that, among 8,613 first-line SGLT-2is matched to 17,226 patients who first were prescribed metformin, SGLT-2is had a similar risk for MI/stroke/mortality (hazard ratio [HR], 0.96; 95% CI, 0.77-1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66-0.97) during a mean follow-up of 12 months.

The authors noted that patients first receiving an SGLT-2i also demonstrated a lower risk for HHF (HR, 0.78; CI, 0.63-0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48-1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with patients receiving metformin.

On the other hand, the authors wrote, patients taking an SGLT-2i as a first-line medication had a higher risk for genital infections (HR, 2.19; CI, 1.91-2.51) but otherwise had a similar safety experience as those receiving metformin.

"Our results suggest that SGLT-2i may be considered as first-line treatment for patients with T2D and cardiovascular disease or who are at increased risk for cardiovascular events," stated lead author HoJin Shin, BPharm, PhD, of the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women's Hospital. "However, more evidence from randomized clinical trials or observational studies will help us to identify patients who would benefit most from using SGLT-2i as first-line type 2 diabetes treatment."

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