Diabetes has proven to significantly worsen the effects of COVID-19 by putting diabetic individuals at greater risk of infection and fatal outcomes. There is a bidirectionality between COVID and diabetes. Individuals suffering from COVID-19 as well as preexisting diabetes can have worsened side effects, leading to a worse prognosis. Furthermore, in some individuals with COVID-19, diabetes was reported even though they had no prior history of diabetes.
In order to decrease the impact of the virus, blood glucose control can help. Metformin is a drug prescribed to diabetic patients for its immune modulation, antiviral, and anti-inflammatory properties. Many of these are symptoms and side effects of COVID-19. In terms of its diabetic benefits, Metformin has a glucose-lowering effect due to the increased glucose uptake by the muscles which decreases the conversion of glycogen to glucose, leading to decreased absorption of glucose from the intestine. Metformin also has benefits towards the COVID-19 virus. Metformin may provide pulmonary protection following SARS-CoV-2 infection. Metformin’s molecular processes show its involvement in pathways controlling inflammation, glucose metabolism, vascular smooth muscle function, and in viral pathogenesis.
The explanation for this is found in the relationship between ACE2 (Angiotensin-converting enzyme 2) and AMPK (Adenosine monophosphate (AMP)-activated protein kinase). ACE2 is an enzyme attached to the membrane of cells located in the intestines, kidney, gallbladder, and heart. Metformin impacts glucose uptake within the intestine where it would interact with the ACE2 enzyme. ACE2 counterbalances the detrimental effect of the ACE/RAS pathway through its downstream axis. AMPK regulates metabolic homeostasis from cellular to whole body levels. AMPK phosphorylates are key molecules in regulating metabolism.
By using the Ingenuity Pathway Analysis tool, an affinity is shown by SARS-CoV-2 to bind to ACE2. The molecular basis for the beneficial effects of metformin on the pulmonary system likely involves metformin activation of AMPK. Metformin can activate AMPK, which phosphorylates ACE2 on Ser-680. This post-translational modification of ACE2 decreases its ubiquitination and therefore extends the half-life of ACE2, which may offer lung protection. Owing to similar interactions between ACE2 to SARS-CoV-1 and SARS-CoV-2, it is reasonable to suspect that metformin may offer similar lung protection in COVID-19.
December 28, 2025