SGLT2 Inhibitors in COVID-19: Umbrella Review, Meta-Analysis, and Bayesian Sensitivity Assessment

Several studies have reported a reduced risk of COVID-19-related mortality in patients taking antidiabetic medications. This is an umbrella review, meta-analysis, and Bayesian sensitivity assessment of SGLT2 inhibitors (SGLT2is) in COVID-19 patients with type 2 diabetes mellitus (T2DM).

A search was conducted on the MEDLINE (PubMed), EMBASE, Cochrane, and ClinicalTrials.gov databases on 5/12/2023. We performed an umbrella review of systematic reviews and meta-analyses on the effects of SGLT2is in T2DM patients with COVID-19 and critically appraised them using AMSTAR 2.0. Trials investigating SGLT2i use in COVID-19 patients post-hospitalisation and observational studies on prior SGLT2i use among COVID-19 patients were included in the meta-analysis, adhering to the PRISMA guidelines.

SGLT2is exhibited significantly lower odds of mortality (OR 0.67, 95% CI 0.53-0.84) and hospitalisation (OR 0.84, 0.75-0.94) in COVID-19 patients with T2DM. Bayesian sensitivity analyses corroborated most of the findings, with differences observed in hospitalisation and mortality outcomes. SGLT-2 inhibitors showed an OR of 1.20 (95% CI 0.64-2.27) for diabetic ketoacidosis. Publication bias was observed for hospitalisation, but not for mortality. The GRADE assessment indicated a low to very low quality of evidence because of the observational studies included.

The prophylactic use of SGLT2is reduces mortality and hospitalisation among COVID-19 patients, particularly in patients with diabetes. The utility of SGLT2is after hospitalisation is uncertain and warrants further investigation. A limited efficacy has been observed under critical conditions. Individualised assessment is crucial before integration into COVID-19 management.