6/28/23, 12:20 AM COVID-OUT (metformin) Pathway Feedback Search Clinical Topics Home Studies COVID OUT (metformin) COVID OUT (metformin) Disease COVID 19 infection Trial question What is the role of metformin in patients with COVID-19 infection? Study design Multi-center Double blinded RCT Population Characteristics of study participants 56.0% female N = 1323 44.0% male 1323 patients (741 female, 582 male) Inclusion criteria: nonhospitalized adults aged between 30 to 85 years with a confirmed diagnosis of COVID-19 within the past 3 days Key exclusion criteria: hospitalization for COVID-19 infection or other reasons; symptom onset > 7 days; immunocompromised patient; hepatic impairment; AUD; history of severe kidney disease Interventions N=663 metformin (immediate-release metformin alone, with an increase in dose over 6 days to 1,500 mg/day for 14 days, or metformin in combination with either fluvoxamine or ivermectin) N=660 placebo (receipt of placebo, fluvoxamine alone or ivermectin alone) Primary outcome Composite outcome of hypoxemia, emergency department visit, hospitalization, or death 27.4 % 27.4 https://web.pathway.md/studies/recz80nKsOgzVrLr9 1/2 6/28/23, 12:20 AM COVID-OUT (metformin) Pathway 23.6 20.5 % 13.7 % 6.8 % No significant difference 0.0 % Metformin Placebo No significant difference in composite outcome of hypoxemia, emergency department visit, hospitalization, or death (23.6% vs. 27.4%; OR 0.84, 95% CI 0.66 to 1.09) Secondary outcomes Borderline significant decrease in composite outcome of emergency department visit, hospitalization, or death (4.1% vs. 7.3%; OR 0.58, 95% CI 0.35 to 0.94) No significant difference in hospitalization or death from any cause (1.2% vs. 2.7%; OR 0.47, 95% CI 0.2 to 1.11) No significant difference in hypoxemia (22.6% vs. 24.3%; OR 0.94, 95% CI 0.72 to 1.22) Conclusion In nonhospitalized adults aged between 30 to 85 years with a confirmed diagnosis of COVID-19 within the past 3 days, metformin was not superior to placebo with respect to the composite outcome of hypoxemia, emergency department visit, hospitalization, or death. Reference Carolyn T Bramante, Jared D Huling, Christopher J Tignanelli et al. Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19. N Engl J Med. 2022 Aug 18;387(7):599- 610. Open reference URL https://web.pathway.md/studies/recz80nKsOgzVrLr9 2/2