Treatment Database

A biguanide antidiabetic agent investigated for Long COVID prevention and ME/CFS treatment. The COVID-OUT RCT demonstrated early metformin use reduced Long COVID incidence by ~41% at 10 months. In ACTIV-6 (Clin Infect Dis 2026; n=2,983 lower-risk outpatients, most with prior immunity), a 14-day course did not meet its primary endpoint of fewer persistent symptoms at 6 months, though clinician-diagnosed Long COVID was less common (0.56% vs 1.17%, a secondary outcome). For established Long COVID, two randomized trials have not shown benefit. In REVIVE-TOGETHER (Annals of Internal Medicine 2026; corrected and republished in October 2026), the metformin dose was lowered from 750 mg to 500 mg twice daily partway through because of side effects, the arm was stopped for futility, and the authors called the metformin results inconclusive. A South Korean trial (Annals of Internal Medicine 2026; n=396) found that 2 weeks of metformin did not improve recovery compared with placebo (63.6% vs 68.2%). Current evidence therefore supports early use during acute infection for prevention, not treatment of established Long COVID.