Does Metformin have a role in Preventing Long COVID?

The post-acute consequences of COVID-19 known as Long COVID is an emerging chronic illness possibly affecting around 10% of those previously infected by the virus. The symptoms associated with Long COVID or Post Acute Sequelae of COVID (PASC) are multivarious and differ from patient to patient, they may range from a single symptom to a serious multi-organ failure. The symptoms can be mild and merciful or chronically life-threatening. The most common symptoms of Long COVID include- fatigue, breathlessness on exertion, persistent cough, muscular and joint pain, deficiencies in hearing and sight, and persistent loss of smell and taste. The study conducted by Bramante et al aimed to assess the outpatient treatment with metformin, ivermectin, or fluvoxamine on Long COVID symptoms.

Bramante and colleagues conducted a multi-site, Phase 3 randomized, quadruple-blinded placebo-controlled trial as outpatient treatment of SARS-CoV-2 that used a 2 x 3 factorial design of parallel treatments. Metformin (used typically in Type 2 Diabetes regimen), Ivermectin (an antiparasitic drug), and Fluvoxamine (an antidepressant drug) were used in this trial called COVID OUT. Participants, care providers, investigators, and outcome assessors were blinded.

Pregnant and lactating women were not excluded. Pregnant and lactating women were randomized 1:1 to metformin or placebo, not fluvoxamine or ivermectin due to less established literature for safety during pregnancy and lactation for those medications.

The study revealed the following finding:

• Of the 1323 randomized trial participants, 8.4% reported a medical provider diagnosed them with Long COVID; cumulative incidence: 6.3% with metformin and 10.6% with matched placebo.
• The metformin effect was consistent across subgroups, including viral variants.
• No statistical difference in Long COVID occurred in those randomized to either ivermectin or fluvoxamine.
• A 42% relative decrease and 4.3% absolute decrease in the Long COVID incidence occurred in participants who received early outpatient COVID-19 treatment with metformin compared to an exact-matching placebo.

References:

Bramante, Carolyn and Buse, John B. and Liebovitz, David and Nicklas, Jacinda and Puskarich, Michael and Cohen, Kenneth R. and Belani, Hrishikesh and Anderson, Blake and Huling, Jared D. and Tignanelli, Christopher and Thompson, Jennifer and Pullen, Matthew and Wirtz, Esteban Lemus and Siegel, Lianne and Proper, Jennifer and Odde, David J. and Klatt, Nichole and Sherwood, Nancy E. and Lindberg, Sarah and Karger, Amy B. and Beckman, Kenneth B. and Erickson, Spencer and Fenno, Sarah and Hartman, Katrina and Rose, Michael and Mehta, Tanvi and Patel, Barkha and Griffiths, Gwendolyn and Bhat, Neeta and Murray, Thomas A. and Boulware, David R., Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months: A Multi-Center, Quadruple-Blind, Parallel Group Randomized Phase 3 Trial. Available at SSRN: https://ssrn.com/abstract=4375620 or http://dx.doi.org/10.2139/ssrn.4375620