Metformin as outpatient treatment for COVID-19 infection is associated with reduced risk for long COVID, according to study results published in The Lancet Infectious Diseases

Researchers conducted a decentralized, randomized, quadruple-blinded, placebo-controlled phase 3 trial at 6 sites in the United States. The researchers assessed the effects of metformin, ivermectin, and fluvoxamine on the risk for long COVID. The primary outcome was severe COVID-19 infection by day 14, and a diagnosis of long COVID was the prespecified, long-term secondary outcome. 

Adults aged 30 to 85 years with overweight or obesity were included in the analysis. All patients had COVID-19 symptoms for less than 7 days and tested positive for SARS-CoV-2 via polymerase chain reaction within 3 days of enrollment. 

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Patients were randomly assigned 1:1:1:1:1:1 via 2×3 parallel factorial randomization to receive either metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. The active follow-up duration was 28 days, and the occurrence of long COVID was assessed over 10 months.

A total of 1126 patients were assessed for long COVID, of whom the median age was 45 (IQR, 37-54) years, 56.1% were women, the median BMI was 29.8 (IQR, 27.0-34.2) kg/m2, and the median time from symptom onset to treatment initiation was 5 (IQR, 4-6) days. Overall, 55% of patients had received primary-series vaccination.

Among all patients, 93 (8.3%) reported a diagnosis of long COVID. At day 300, the cumulative incidence of long COVID was 6.3% among patients who received metformin vs 10.4% among those who received matched placebo (hazard ratio [HR], 0.59; 95% CI, 0.39-0.89; P =.012). 

[T]aking the next steps to implement metformin as a COVID-19 treatment to prevent long COVID is an urgent public health need.

Further analysis showed metformin was more effective for reducing the risk for long COVID when initiated less than 4 days (HR, 0.37; 95% CI, 0.15-0.95) vs 4 days or longer (HR, 0.64; 95% CI, 0.40-1.03) after symptom onset. 

Ivermectin and fluvoxamine had no significant effect on the incidence of long COVID, with similar results observed after adjustment for vaccination status. 

Limitations of this study include potential selection bias and the exclusion of patients at low risk for severe COVID-19 infection. 

According to the researchers, “[T]aking the next steps to implement metformin as a COVID-19 treatment to prevent long COVID is an urgent public health need.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Infectious Disease Advisor