Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19

Carolyn T. Bramante*, Jared D. Huling, Christopher J. Tignanelli, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Kenneth Cohen, Michael A. Puskarich, Hrishikesh K. Belani, Jennifer L. Proper, Lianne K. Siegel, Nichole R. Klatt, David J. Odde, Darlette G. Luke, Blake Anderson, Amy B. Karger, Nicholas E. Ingraham, Katrina M. Hartman, Via Rao, Aubrey A. HagenBarkha Patel, Sarah L. Fenno, Nandini Avula, Neha V. Reddy, Spencer M. Erickson, Sarah Lindberg, Regina Fricton, Samuel Lee, Adnin Zaman, Hanna G. Saveraid, Walker J. Tordsen, Matthew F. Pullen, Michelle Biros, Nancy E. Sherwood, Jennifer L. Thompson, David R. Boulware, Thomas A. Murray

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


BACKGROUND Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARSCoV-2 vaccination and receipt of other trial medications. RESULTS A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P=0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P=0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P=0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19.

Original languageEnglish (US)
Pages (from-to)599-610
Number of pages12
JournalNew England Journal of Medicine
Issue number7
StatePublished - Aug 18 2022

ASJC Scopus subject areas

  • General Medicine


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