Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19: A Systematic Review and Network Meta-analysis.

Importance: Patients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality. Objective: To evaluate the association between COVID-19-related adverse outcomes and 8 antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19. Data Sources: Data were retrieved and collected in PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov from database inception to September 5, 2022. Study Selection: For this systematic review and network meta-analysis, randomized clinical trials and observational studies conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection were included after blinded review by 2 independent reviewers and consultations of disagreement by a third independent reviewer. Of 1802 studies initially identified, 31 observational studies met the criteria for further analysis. Data Extraction and Synthesis: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Bayesian network meta-analyses were performed with random effects. Main Outcomes and Measures: A composite adverse outcome, including the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, or in-hospital death. Results: Thirty-one distinct observational studies (3 689 010 patients with diabetes hospitalized for COVID-19) were included. The sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were associated with relatively lower risks of adverse outcomes compared with insulin (log of odds ratio [logOR], 0.91; 95% credible interval [CrI], 0.57-1.26), dipeptidyl peptidase-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and glucosidase inhibitors (logOR, 0.50; 95% CrI, 0.00-1.01). Based on the surface under the cumulative ranking curves value, SGLT-2is were associated with the lowest probability for adverse outcomes (6%), followed by glucagon-like peptide-1 receptor agonists (25%) and metformin (28%). A sensitivity analysis revealed that the study was reliable. Conclusions and Relevance: These findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19-related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes.