Type 2 diabetes is considered an important risk factor for a severe course of COVID-19 and is associated with a mortality rate almost twice as high as in metabolically healthy patients. It is relatively unclear what role antidiabetic drugs play in this process. The administration of metformin, for example, could have a more beneficial effect.
The risk factors for an unfavorable course of COVID-19 in diabetics are old age, obesity, and poor blood glucose control - but little is known about the influence of treatment drugs, writes A. J. Scheen from the Division of Diabetes, Nutrition and Metabolic Disorders at the University of Liège (Belgium) in a review.
Metformin has been the most commonly used oral anti-diabetes drug for 20 years, and up to three-quarters of patients with type 2 diabetes take the drug alone or in combination. The UKPDS study already showed that metformin can reduce mortality in newly diagnosed type 2 diabetics with obesity, and obesity is also a major risk factor for severe COVID-19 cases.
There is some evidence that metformin could have a positive effect on COVID-19 via several mechanisms. These include:
However, some authors also express concern that the administration of metformin could lead to increased lactic acidosis in COVID-19 patients with multiple organ failure.
Four retrospective observational studies investigated the possible influence of metformin on the course of severe COVID-19 disease. In a US study of 6,256 in-patients (mean age 75 years), the use of metformin showed a significant reduction in mortality in women - but not in men. In the CORONADO study from France, patients taking metformin before hospital admission had lower mortality in the first seven days (OR 0.59) - but in the multivariate analysis, only a non-significant trend was seen (OR 0.80). In two other smaller trials from China, the hospital mortality of metformin users was also significantly lower than in patients without this drug. The meta-analysis of all four trials showed a 25% reduction in mortality for metformin users.
However, the author warns against drawing hasty conclusions from the results. As with all observational studies, possible influencing factors cannot be excluded with certainty. It is conceivable, for example, that among the non-users there are more patients with contraindications to metformin and thus also more elderly people and patients with renal insufficiency, who per se have a higher risk of an unfavorable COVID-19 course. On the other hand, metformin is mainly used for overweight and obesity, which is a risk factor for COVID-19. In any case, it can be assumed that there is no safety risk against the continued use of metformin in COVID-19 patients - except perhaps in patients with severe gastrointestinal symptoms, hypoxia, and/or multiple organ failure.
“Only controlled randomized trials could provide final certainty about the benefit of metformin in COVID-19. But it is unlikely that any company will be able to do these trials with the cheap generic drug," said Scheen.
Source:
A.J. Scheen; Metformin and COVID-19: From cellular mechanisms to reduced mortality; Diabetes & Metabolism