Low-dose dapagliflozin (5 mg) was associated with a 30% increased risk of heart failure hospitalization compared with empagliflozin, while the 10-mg dose did not show this elevated risk, according to a recent study.

Researchers conducted a comparative effectiveness study to evaluate cardiovascular and safety outcomes associated with individual sodium-glucose cotransporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes (T2D). In the study, published in JAMA Internal Medicine, the researchers employed a target trial emulation using three large U.S. claims databases: Optum Clinformatics, MarketScan, and Medicare. The cohort included 232,890 patients initiating canagliflozin, 129,881 initiating dapagliflozin, and 295,043 initiating empagliflozin, with follow-up extending up to 8 years.

To address potential confounding, the researchers used propensity score weighting across 129 covariates. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards models, with results pooled across databases via fixed-effect meta-analysis.

For cardiovascular outcomes, the risk of myocardial infarction or stroke was comparable between canagliflozin (HR = 0.98, 95% CI = 0.91–1.05) and dapagliflozin (HR = 0.95, 95% CI = 0.89–1.03) relative to empagliflozin, noted lead study author HoJin Shin, BPharm, PhD, of the Division of Pharmacoepidemiology and Pharmacoeconomics in the Department of Medicine at Brigham and Women’s Hospital and Harvard Medical School, and colleagues. However, dapagliflozin initiators had a significantly increased risk of heart failure–related hospitalization (HR = 1.19, 95% CI = 1.02–1.39), particularly at the 5-mg dose (HR = 1.30, 95% CI = 1.12–1.50), whereas canagliflozin and empagliflozin demonstrated similar risk profiles.

For safety outcomes, canagliflozin was associated with a reduced risk of genital infections (HR = 0.94, 95% CI = 0.91–0.97) but an increased risk of severe urinary tract infections (HR = 1.13, 95% CI = 1.03–1.24). Dapagliflozin users had lower risks of both genital infections (HR = 0.92, 95% CI = 0.89–0.95) and diabetic ketoacidosis (HR = 0.78, 95% CI = 0.68–0.90). No statistically significant differences in bone fractures or lower-limb amputations were observed among the three agents.

While SGLT-2 inhibitors showed comparable cardiovascular effectiveness, only dapagliflozin 5 mg was associated with a significantly higher risk of heart failure hospitalization compared with empagliflozin (HR = 1.30, 95% CI = 1.12–1.50), whereas the 10-mg dose did not demonstrate this increased risk. Safety profiles varied slightly, but overall risk-benefit comparisons were similar among the three agents.

Full disclosures can be found in the published study.