medwireNews: People who start sodium-glucose cotransporter (SGLT)2 inhibitors as a first-line diabetes treatment have a reduced risk for heart failure hospitalization relative to those who start metformin and a similar risk for other vascular outcomes, a study shows.
The population-based study with time-stratified propensity-score matching was designed to “emulate a target trial comparing the risk for cardiovascular events associated with first-line SGLT-2 [inhibitors] versus metformin in real-world patients with [type 2 diabetes],” explain the researchers.
But a randomized clinical trial “is warranted to establish more robust evidence,” they write in the Annals of Internal Medicine.
The matched cohort, identified in US insurance claims data, comprised 8613 people who initiated an SGLT2 inhibitor as a first-line treatment and 17,226 who started metformin between 2013 and 2020.
The incidence rate of myocardial infarction or stroke plus mortality was 15.0 per 1000 person–years during an average 10.7 months of treatment with SGLT2 inhibitors and 16.2 per 1000 person–years during an average 12.2 months of treatment with metformin, with no significant difference between the treatments.
The rate of myocardial infarction as an individual endpoint was numerically lower in people taking SGLT2 inhibitors versus metformin, at 4.9 versus 7.2 per 1000 person–years, but the difference did not reach statistical significance (hazard ratio [HR]=0.70, confidence interval 0.48–1.00).
Conversely, the rates per 1000 person–years of heart failure hospitalization or all-cause mortality were 18.3 versus 23.5 with SGLT2 inhibitors versus metformin, which was a significant difference favoring the former treatment (HR=0.80).
The heart failure benefits of SGLT2 inhibition versus metformin first appeared after about 6 months, say HoJin Shin (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA) and study co-authors.
Safety outcomes were similar between the two treatments with the exception of genital infections, which occurred at an incidence rate per 1000 person–years of 54.1 in people taking SGLT2 inhibitors and 23.7 in those taking metformin, which was a significant and more than doubled risk associated with SGLT2 inhibition.
However, the researchers argue that genital infections “may be less serious” than other safety outcomes, which included acute kidney injury, severe hypoglycemia, and diabetic ketoacidosis, “and can be appropriately managed.”
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Ann Intern Med 2022; doi:10.7326/M21-4012