Summary: In 1250 patients hospitalised with COVID-19 and cardiometabolic risk factors (50.9% with type 2 diabetes), dapagliflozin 10 mg daily was well tolerated and safe irrespective of diabetes status. The organ-dysfunction-or-death prevention outcome was not significantly reduced (with diabetes 10.9% vs 13.9%, HR 0.76, 95% CI 0.49 to 1.18; without diabetes 11.5% vs 13.3%, HR 0.86, 95% CI 0.55 to 1.35), and serum biomarkers remained stable.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1250 adults hospitalised with COVID-19 and cardiometabolic risk factors (T2D in 636, 50.9%); prespecified subgroup analysis of the DARE-19 double-blind randomised trial, conducted across multiple international sites (NCT04350593). |
| Intervention | Dapagliflozin 10 mg once daily, initiated during acute COVID-19 hospitalisation (approximately n=625). |
| Comparison | Matching placebo once daily (approximately n=625). |
| Outcome | Prevention (new or worsened organ dysfunction or death by day 30): with T2D 10.9% vs 13.9%, HR 0.76 (95% CI 0.49 to 1.18); without diabetes 11.5% vs 13.3%, HR 0.86 (95% CI 0.55 to 1.35); subgroup interaction p=0.668, all confidence intervals crossing 1 (no significant benefit). Recovery (clinical-status hierarchical composite, day 30): no significant difference, interaction p=0.222. Serum bicarbonate, eGFR and haematocrit were comparable between arms regardless of diabetes status. Serious adverse events: with T2D 12.7% (dapagliflozin) vs 14.3% (placebo); without diabetes 8.5% vs 11.9%. Diabetic ketoacidosis occurred in 2 dapagliflozin-treated patients with T2D. No absolute risk reduction or NNT is interpretable given the non-significant effect estimates. |
Dapagliflozin in hospitalised COVID-19, by diabetes status
RCT subgroup analysis · DARE-19 · day 30
Dapagliflozin started during COVID-19 hospitalisation was safe and well tolerated regardless of type 2 diabetes status, but no significant prevention benefit was shown; both subgroup hazard ratios crossed 1.
Expert Commentary
This prespecified subgroup analysis of DARE-19 was designed to test whether the safety and efficacy of dapagliflozin differed by type 2 diabetes status, and its honest verdict is a safety result rather than an efficacy one. The point estimates for the prevention outcome numerically favoured dapagliflozin in both subgroups, but every confidence interval crossed 1 and the interaction p-values were non-significant, so no treatment benefit was demonstrated. What can be said with reasonable confidence is that initiating an SGLT2 inhibitor during acute COVID-19 was not accompanied by metabolic or renal harm: bicarbonate, eGFR and haematocrit tracked together across arms, serious adverse events were no more frequent with active drug, and ketoacidosis was rare. The principal limitation is statistical power, because this secondary analysis was not sized to detect subgroup effects and the parent trial itself missed its primary efficacy endpoint, so absence of a signal here should not be read as evidence of efficacy. The pronounced manufacturer involvement, with AstraZeneca employees among the authors and as trial sponsor, further warrants cautious interpretation of any favourable framing. Can I use this with my patients? Not yet as a COVID-19 treatment, but the data are reassuring for clinicians who must decide whether to continue an SGLT2 inhibitor in a stable, well-monitored inpatient with type 2 diabetes who is hospitalised with an acute non-cardiovascular illness. Adequately powered trials would be needed before any therapeutic claim could be entertained.
References
Abdel Jawad M, Furtado RHM, Esterline R, Oscarsson J, Gasparyan SB, Koch GG, et al. Efficacy and safety of dapagliflozin in patients hospitalized with COVID-19 with and without type 2 diabetes: a prespecified analysis of the DARE-19 randomized trial. Cardiovasc Diabetol. 2025;24(1):307. doi:10.1186/s12933-025-02875-6