Metformin for Diabetes Has No Effect on COVID-19 Infection, Death

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Prescription of metformin does not influence susceptibility to COVID-19 or COVID-19 mortality, a large primary care-based study suggests.

The findings were published online February 9 in the Journal of Clinical Endocrinology and Metabolism by Jingya Wang, PhD, of the University of Birmingham, UK, and colleagues.

In the study, the first to examine the effects of metformin use in nonhospitalized patients with COVID-19, prescription of metformin did not influence susceptibility to COVID-19, or death from it or any cause.

“This is reassuring, given that patients with diabetes are more susceptible to mortality with COVID-19, and that metformin is the most commonly prescribed glucose-lowering medication. Optimizing glycemic control should continue to be the best advice for patients with diabetes, especially if rates of COVID-19 rise,” Wang and colleagues write.

The results contrast with prior observational data from hospitalized patients showing a mortality benefit among those taking metformin prior to developing COVID-19. There was limited adjustment for confounders in these studies and some included patients without diabetes, the authors note.

Taken together, they say, the data “demonstrate that patients who are prescribed long-term metformin and are currently well can be reassured that it is safe to continue consumption.”

However, sick-day rules are strongly advised for any illness that increases the risk for dehydration, including COVID-19.

“Clinicians should advise patients taking metformin who develop symptoms consistent with COVID-19 — or indeed any infection — to withhold this medication if there are concerns about acidosis and consider increased monitoring of blood glucose for the duration of the illness,” they write.

No Differences in COVID-19 Outcomes With Matched Groups

The study involved 29,558 individuals with a current prescription for metformin plus at least one other glucose-lowering drug and 10,271 with a current prescription for at least one other glucose-lowering agent but not metformin. There were 10,183 individuals in each group after propensity matching for confounders including sociodemographic factors (age and sex, body mass index and other metabolic profile measures, blood pressure, and cardiovascular and other comorbidities).

Participants were followed from January 30, 2020 until either reaching a study outcome including death, an individual left the practice, the practice left the database, or study end, on October 13, 2020.

With propensity matching, suspected or confirmed COVID-19 occurred in 172 individuals in the metformin group and 186 in the no metformin group, corresponding to crude incidence rates of 24.7 and 26.8 per 1000 person-years, respectively.

Primary care consultations for confirmed or suspected COVID-19 were less common among those taking metformin, with an adjusted hazard ratio of 0.85, which was not significant. The difference for confirmed COVID-19 cases also didn’t reach statistical significance, with an adjusted hazard ratio of 0.80.

Following propensity score matching, 17 of 214 deaths in the metformin-treated group and 20 of 266 deaths in the no metformin group were COVID-19 related. There were no significant differences between groups in all-cause mortality (adjusted hazard ratio, 0.89) or COVID-19 related death (0.87).

A negative outcome control analysis suggested there was no unobserved confounding.

The authors have reported no relevant financial relationships.

J Clin Endocr Metab. Published online February 9, 2021. Abstract

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