Metformin may reduce risk for long COVID among adults with obesity
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Key takeaways:
- Adults who received metformin after being diagnosed with COVID-19 had a reduced risk for developing long COVID.
- Ivermectin and fluvoxamine were not associated with a reduction in long COVID risk.
Adults with overweight or obesity who received metformin shortly after a COVID-19 diagnosis had a lower risk for developing long COVID than those receiving placebo, according to study data.
“Early outpatient COVID-19 treatment with metformin decreased the subsequent risk of long COVID by 41.3% during 10-month follow-up,” Carolyn T. Bramante, MD, MPH, assistant professor of medicine in the adult and pediatric weight management clinics, division of geriatrics, palliative and primary care at the University of Minnesota, and colleagues wrote. “This finding is consistent with the 42.3% reduction in health care utilization for severe COVID-19 with metformin in the first 14 days of the trial. Fluvoxamine and ivermectin did not decrease the risk of long COVID.”
Bramante and colleagues conducted a randomized, quadruple-blind, placebo-controlled trial in which adults aged 30 to 85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented positive COVID-19 test were enrolled at six study sites in the U.S. Participants were randomly assigned, 1:1:1:1:1:1, using a 2x3 factorial design, to metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo or placebo plus placebo. All study drugs were oral medications in tablet form. Follow-up surveys were conducted every 30 days up to day 300 beginning 60 days after randomization. Participants were defined as having long COVID if they received a diagnosis from a medical provider. Long COVID was ascertained through follow-up studies on day 180, 210, 240, 270 and 300.
There were 1,126 adults included in the study (56.1% women; median age, 45 years), of whom 564 received metformin and 562 matched placebo; 361 received ivermectin and 378 matched placebo, and 297 received fluvoxamine and 298 matched placebo. Each person in the trial contributed to two comparisons after factorial design was opened.
Of the cohort, 8.3% were diagnosed with long COVID by day 300. Adults who received metformin were less likely to be diagnosed with long COVID than those who received matched placebo (HR = 0.59; 95% CI, 0.39-0.89; P = .012). Ivermectin and fluvoxamine were not associated with a difference in long COVID risk compared with matched placebo.
The reduced risk for long COVID with metformin therapy was consistent across subgroups and COVID-19 variants. When metformin was initiated less than 4 days after symptom onset, adults had an even greater reduction in long COVID risk compared with placebo (HR = 0.37; 95% CI, 0.15-0.95).
The timing of long COVID diagnoses did not change during the trial. The percentage of adults diagnosed with long COVID was higher among women than men (10.9% vs. 4.9%). A higher percentage of unvaccinated adults were diagnosed with long COVID compared with those who received at least the primary vaccine series (10.3% vs. 6.6%). Among 57 adults who received a booster vaccination, one reported a long COVID diagnosis.
“As the COVID-19 pandemic continues to evolve, all therapeutics require further prospective, interventional trials to assess long COVID incidence, including among people who have received vaccination and booster vaccination, and people with previous SARS-CoV-2 infection,” the researchers wrote. “Long COVID is an important public health emergency that might have lasting health, mental health, and economic sequelae, particularly in socioeconomically marginalized groups, and metformin is safe and widely available at low cost.”
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