SGLT2 inhibitors did not lead to lower 28-day all-cause mortality compared with usual care or placebo in patients hospitalized with COVID-19, according to findings from a meta-analysis presented at ESC Congress 2023.

Members of the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies Working Group conducted the meta-analysis using aggregate data from the DARE-19, RECOVERY and ACTIV-4A trials, each of which evaluated efficacy of SGLT2 inhibitors in patients hospitalized with COVID-19 compared with usual care or placebo. Overall, these trials randomized 6,096 participants to SGLT2 inhibitors (n=3,025) and to usual care or placebo (n=3,071), across the US, UK, Brazil, Canada, Mexico, Argentina, India, Spain, Nepal, Indonesia, Vietnam, South Africa and Ghana. The average age of participants ranged between 62 to 73 years, 39% were women and 25% had type 2 diabetes at the time of randomization.

At 28 days post-randomization, there were 351 deaths among patients in the SGLT2 inhibitor group compared with 382 deaths in the usual care or placebo group. The summary odds ratio was 0.93 for SGLT2 inhibitors, with consistency across trials – a finding that corresponded to an absolute mortality risk of 11.7% for SGLT2 inhibitors compared with an assumed mortality risk of 12.4% for usual care or placebo, according to the researchers.

In other findings, data on in-hospital and 90-day all-cause mortality were only available for the DARE-19 and ACTIV-4A trials, but the results were similar. Similarly, there was no significant difference observed in terms of progression to acute kidney injury, requirement for dialysis or death and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation or death at 28 days. The primary safety outcome of ketoacidosis by 28 days was observed in seven patients allocated to SGLT2 inhibitors and two patients assigned to usual care or placebo.

"We found no convincing evidence that administration of SGLT2 inhibitors, compared with usual care or placebo, reduces 28-day all-cause mortality, or improves other pre-specified efficacy outcomes," said Mikhail Kosiborod, MD, FACC, of Saint Luke's Mid America Heart Institute in Kansas City. "These findings do not support the use of SGLT2 inhibitors as standard care in this clinical setting. No new safety signals were observed with the use of SGLT2 inhibitors in this patient population, and their routine discontinuation during acute illness for patients that receive them for other indications such as heart failure, chronic kidney disease, or type 2 diabetes does not appear to be warranted."

Clinical Topics: COVID-19 Hub, Dyslipidemia, Lipid Metabolism

Keywords: ESC Congress, ESC23, ACC International, Sodium-Glucose Transporter 2 Inhibitors, Sodium-Glucose Transporter 2, Prospective Studies, COVID-19

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