Metformin therapy and mortality: Hypoglycemic drugs may influence the pathogenesis of COVID-19 and may have implications for the treatment of patients with diabetes and COVID-19.

Diabetes is an epidemic with many complications and presents a major global health threat. The International Diabetes Federation has determined that one in 11 adults has diabetes. The presence of diabetes, varying degrees of hyperglycemia, and general complications of diabetes are associated with the severity and increased mortality in COVID-19. Hyperglycemia can modulate immune and inflammatory responses, predisposing patients to severe COVID -19 and possibly fatal outcomes. Hypoglycemic drugs may influence the pathogenesis of COVID-19 and could have implications for the treatment of patients with diabetes and COVID-19. Dipeptidyl peptidase (DPP4) and renin-angiotensin-aldosterone (RAAS) systems are genetically linked to the risk of infection with SARS-CoV-2. Glucagon-like peptide 1 (GLP1) analogues are not a good option for COVID-19 patients because they will need more time to become effective. Sodium-glucose cotransporter 2 (SGLT2) inhibitors may produce side effects such as osmotic diuresis and dehydration in patients with COVID-19, and therefore cannot be recommended.

Researchers have intensely studied the relationship between metformin and COVID-19. However, knowledge in this area is evolving rapidly and many publications appear frequently. The present study performed a meta-analysis to detect the overall influence of metformin treatment on COVID-19 patients with diabetes. The odds ratio correlated with the 95% confidence interval determined the effectiveness of metformin on COVID-19 patients with diabetes. The Q test and I2 Statistics assessed statistical heterogeneity between studies. In the absence of apparent heterogeneity, the fixed-effects model (the Mantel-Haenszel method) approximated the summary odds ratio. Otherwise, random effects models (the Dersimonian and Lair method) were used. Ultimately, the random-effects models evaluated the overall odds ratio estimates and the 95% confidence interval to determine the effect of metformin on mortality and severity in patients with COVID-diabetes. 19. Logistic meta-regression analyzes analyzed the origins of heterogeneity between studies. The funnel plot and Beggs’ row association method determined publication bias. STATA 12.0 software performed statistical analyzes.

The researchers gathered 17 studies that included 20,719 COVID-19 patients with diabetes. The results indicated that metformin was linked to a significantly lower death rate and severity in COVID-19 patients with diabetes. Omission of a study in a general meta-analysis analyzed over time; removing all research did not create any significant difference, proving that the results were statistically reliable. COVID-19 has spread widely with a substantial impact on most countries. Therapeutic methods in patients with COVID-19 with diabetes are limited. Diabetes has been linked to poor outcomes in COVID-19 patients. An earlier meta-analysis showed that treatment with metformin correlated with decreased mortality in COVID-19 patients with diabetes.

Metformin may promote lifespan and facilitate health through mitohormesis and lysosomal pathways to synchronize mTORC1 and AMPK. In addition, metformin contains anti-inflammatory properties and reduces oxidative damage. The ability of metformin to lower neutrophil count and reduce extracellular traps has also been suggested as potential mechanisms for its benefits in patients with diabetes and COVID-19.

Acute respiratory distress syndrome (ARDS) is one of the most common complications in patients with COVID-19. Prevention of ARDS is essential to facilitate the outcome of patients. The influence of metformin on ARDS creates controversy. Metformin was significantly linked to a reduction in heart failure and inflammation. However, some research has not found reliable results from the use of metformin on the clinical severity of the disease. An additional study determined that diabetes treatment with metformin was linked to an increased risk of disease progression in COVID-19 patients with diabetes during hospitalization. The results with accumulated data showed that metformin was linked to significantly reduced severity in COVID-19 patients with diabetes.

The study has some limitations, such as heterogeneity between studies in general comparisons. Although the study did not find any factors that could influence the original heterogeneity, the heterogeneity could affect the results. In conclusion, the meta-analysis showed that following metformin treatment in COVID-19 diabetic patients could reduce mortality and severity. However, the use of metformin was significantly linked to a greater likelihood of acidosis, especially in severe cases of COVID-19. Therefore, patients with severe COVID-19 should be monitored closely for signs of developing lactic acidosis, acidosis, and reduced kidney function.

Practice the beads:

  • COVID-19 has spread around the world, affecting millions of people and causing more than 3.7 million deaths worldwide.
  • Metformin was linked to significantly reduced mortality in COVID-19 patients with diabetes.
  • People with severe COVID-19 should be monitored closely for signs of lactic acidosis, acidosis and kidney failure.

Yang, Wenxing et al. “The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus. ” Diabetes Research and Clinical Practice, flight. 178 108977. July 22, 2021.

Wang, Jingya et al. “Association of metformin with Susceptibility to COVID-19 in people with type 2 diabetes. ” The Journal of Clinical Endocrinology and Metabolism flight. 106.5 05. April. 2021.

Emmanuella Louissaint, PharmD candidate, Faculty of Pharmacy LECOM


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