Overweight/obese adults with symptomatic COVID-19 treated with metformin are less likely to develop long COVID (COVID-OUT)

Reference

Bramante CT, Buse JB, Liebovitz DM, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis 2023;S1473-3099(23)00299-2.

Synopsis

In this complex study funded by foundations and government agencies, 1126 overweight or obese adult outpatients with symptomatic, laboratory-confirmed COVID-19 were randomized to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Ivermectin was administered for 3 days (390-470 μg/kg per day). Metformin, administered for 14 days, was titrated to 1500 mg daily. Fluvoxamine, also used for 14 days, was titrated to 50 mg twice daily. The primary outcome of the study was the development of severe COVID-19 by day 14. This report evaluates the role of metformin in the development of long COVID (self-reported as diagnosed by a medical provider) during 6 months of follow-up. This is potentially problematic for many reasons including the lack of a standard diagnosis for long COVID and the lack of confirmation of the self-report. Overall, 6.2% of adults who received metformin and 10.3% of adults who received placebo reported a diagnosis of long COVID (number needed to treat = 25; 95% CI 14 - 112), but neither ivermectin nor fluvoxamine had any effect. The authors report no difference in adverse events among treatment groups.