Written by Babatunde Carew
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Canagliflozin and dapagliflozin demonstrated similar cardiovascular protection and safety profiles when compared to empagliflozin in patients with type 2 diabetes.
SGLT-2 showdown
SGLT2 inhibitors have been on a tear, with study after study demonstrating effectiveness in cardiorenal protection in key demographics. However, many of the landmark studies (EMPA-REG , EMPEROR, DAPA-HF) were placebo controlled, so comparative safety and efficacy among these agents is difficult to quantify. This observational study used U.S. claims data to compare cardiovascular and safety outcomes among approximately 658,000 adults with type 2 diabetes newly prescribed canagliflozin or dapagliflozin versus empagliflozin. The rate of MI/stroke was similar among all agents, but low-dose dapagliflozin had a higher heart failure hospitalization risk compared to empagliflozin (HR 1.30; 95% CI, 1.12–1.50). While there were modest differences in safety outcomes (lower risk of genital infection for canagliflozin and dapagliflozin vs. empagliflozin, for example), overall risk for safety events was similar among all agents. Limitations in this study include the lack of data on cardiovascular deaths in the utilized databases and potential confounding due to unmeasured variables such as duration and severity of diabetes or known cardiovascular disease.
How will this change my practice?
This study reinforces my current practice of prescribing whichever SGLT2 inhibitor is covered by insurance for patients with type 2 diabetes and elevated cardiovascular risk, as all agents demonstrated comparable cardiovascular benefits and safety profiles. While empagliflozin showed a slight advantage over low-dose dapagliflozin in reducing heart failure hospitalizations, this difference diminished with up-titration to the 10 mg dose, highlighting the importance of using the higher dose of dapagliflozin when targeting cardiovascular risk reduction.
Source
Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors. JAMA Intern Med. 2025 Mar 1;185(3):302-313. doi: 10.1001/jamainternmed.2024.7357. PMID: 39836397
