ContagionLive Findings from a growing body of randomized trials and real-world analyses show that starting metformin during acute SARS-CoV-2 infection is safe and significantly reduces the risk of developing long COVID. As the global health community continues to grapple with the long-term consequences of SARS-CoV-2 infection, preventing post–COVID-19 condition—commonly known as long COVID—has become a clinical priority. New evidence from randomized trials and target trial emulations suggests that an unlikely candidate, metformin, may offer a practical and effective strategy to reduce this risk when started early in acute infection.
Chaichana and colleagues recently conducted a sequential trial emulation to assess whether initiating metformin after SARS-CoV-2 infection lowers the risk of long COVID. Their findings closely align with results from randomized clinical trials, providing important validation across study designs. Together with data from earlier trials, these data strengthen the case for offering metformin to nonhospitalized adults with acute COVID-19 to prevent long-term sequelae.
At first glance, repurposing a chronic diabetes medication for an acute viral illness may seem counterintuitive. However, metformin’s history reveals a broader pharmacologic profile. Early work on biguanides in the early 20th century explored antiviral and antimalarial applications. Although phenformin and buformin were eventually abandoned due to lactic acidosis risk, metformin emerged as a safer alternative and became widely used for type 2 diabetes. Over time, findings from studies demonstrated its anti-inflammatory and immunometabolic effects, along with reassuring safety data showing no increased risk of lactic acidosis when used appropriately.
Interest in metformin as an antiviral agent reemerged in the 2000s, driven by findings from in vitro studies showing host-directed antiviral activity. When SARS-CoV-2 emerged in 2020, results from observational studies, computational modeling, and laboratory experiments further supported its potential role in acute COVID-19 treatment. Given its low cost, global availability, tolerability, and lack of need for laboratory monitoring during short-term use, metformin was well suited for clinical testing.