Metformin might protect women with type 2 diabetes against COVID-19 mortality
medwireNews: An observational study suggests that prior metformin use may offer a protective effect against COVID-19 mortality in people with type 2 diabetes, but only for women.
The study included 6256 patients (52.8% women) with type 2 diabetes or obesity who were admitted to US hospitals with COVID-19. Among the cohort overall, there was a tendency for metformin users to have a lower mortality risk than nonusers, at 16.9% versus 20.2%, but this was not statistically significant in unadjusted or adjusted analyses.
However, Carolyn Bramante (University of Minnesota, Minneapolis, USA) and co-researchers hypothesized that the effects of metformin would be stronger in women than men, because of “the sex-specific anti-inflammatory effects of metformin,” including a greater reduction of tumor necrosis factor α in women than men.
As reported in The Lancet Healthy Longevity, metformin use was associated with a statistically significant reduction in mortality risk of around 20–25% among women, including in a propensity-matched model, whereas there was no detectable difference in men.
Almost all of the study participants had type 2 diabetes, yet less than half of the cohort had a prior prescription for metformin. Specifically, 99.3% of the 2333 people with at least a 90-day prescription for metformin in the 12 months before their COVID-19 diagnosis had type 2 diabetes, as did 94.8% of the 3923 people without a prescription.
The presence of obesity was recorded for 4.8% and 9.0% of the metformin and no metformin group, respectively, with no BMI group recorded for the other study participants.
In a linked commentary, Angela Dardano and Stefano Del Prato, both from the University of Pisa in Italy, write: “Although other retrospective studies have suggested a potential benefit of metformin this gender effect was not previously reported.”
The commentators note that a protective effect of metformin would be consistent with the increasing evidence, albeit largely indirect, for its pleiotropic effects. But they also point out the many limitations of the observational study design, including the inability to determine which participants were actually taking metformin at the time of SARS-CoV-2 infection, and to fully account for confounders.
Randomized, controlled trials would be difficult to do in the current environment and unlikely to attract funding “because of the lack of consistent investment in a potentially powerful, yet out-of-patent, drug,” say Dardano and Del Prato.
“However, it is because of the low cost of metformin that randomised trials could prove a very high cost-effectiveness, particularly when dealing with highly expensive diseases, such as COVID-19,” they conclude.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group