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

Abstract Background: 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 in COVID-19 patients with type 2 diabetes mellitus (T2DM). Methods: A search was conducted in 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 SGLT2i effects 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. Results: SGLT2 inhibitors 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 observational studies. Conclusions: Prophylactic use of SGLT2 inhibitors reduces mortality and hospitalization among COVID-19 patients, particularly in diabetic patients. The utility of SGLTi after hospitalization is uncertain and warrants further investigation. Limited efficacy has been observed under critical conditions. Individualized assessment is crucial before integration into COVID-19 management.