Study participants who received metformin for outpatient therapy of COVID-19 had lower rates of long COVID than those who received placebo.

Various antiviral therapies can reduce COVID-19 progression in high-risk outpatients, but none have been definitively shown to reduce symptoms or signs persisting after acute infection (i.e., long COVID). In a randomized trial, investigators now report the effect of metformin on incidence of long COVID. Participants were overweight or obese adults with COVID-19 symptoms for <7 days. They were assigned to receive metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. This analysis focused on 1126 participants (median age, 45; 56% women, 55% had received COVID-19 vaccination) who received metformin or matched placebo.

Findings are as follows:

• 93 participants (8.3%) reported that a medical provider had made a diagnosis of long COVID by day 300.
• Cumulative incidence of long COVID was 6.3% (metformin) and 10.4% (placebo), a difference translating to a 41% reduction with metformin.
• Neither ivermectin nor fluvoxamine reduced incidence of long COVID.

Comment

The data in this study are intriguing, but I do not find them definitive enough to recommend using metformin to prevent long COVID. A key challenge in assessing the effects of treatment on long COVID is lack of consensus on how to diagnose the condition; indeed, in this study the diagnosis was not based on specific criteria but was made at the discretion of the participant’s medical provider. Recent progress in defining long COVID is based on a prospective study in the RECOVER cohort (JAMA 2023; 329:1934. opens in new tab). One of the highest research priorities is to apply consensus definitions to prospectively assess whether (and which) therapies will prevent long COVID.