The SA Journal Diabetes & Vascular Disease Volume 18 No 2 (November 2021)

VOLUME 18 NUMBER 2 • November 2021 29 SA JOURNAL OF DIABETES & VASCULAR DISEASE Diabetes news Metformin may reduce mortality risk three-fold in patients with COVID-19 and diabetes U se of the diabetes drug metformin, before a diagnosis of COVID-19, is associated with a three-fold decrease in mortality in COVID-19 patients with type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. Diabetes is a significant co-morbidity for COVID-19. ‘This beneficial effect remained, even after correcting for age, sex, race, obesity and hypertension or chronic kidney disease and heart failure,’ said Dr Anath Shalev, director of UAB’s Comprehensive Diabetes Centre and leader of the study. ‘Since similar results have now been obtained in different populations from around the world, including China, France and a UnitedHealthcare analysis. This suggests that the observed reduction in mortality risk associated with metformin use in subjects with type 2 diabetes and COVID-19 might be generalisable,’ Shalev said. How metformin improves prognosis in the context of COVID- 19 is not known, Shalev says. The UAB findings suggest that the mechanisms may go beyond any expected improvement in glycaemic control or obesity, since neither body mass index, blood glucose nor haemoglobin A 1c were lower in the metformin users who survived compared to those who died. ‘The mechanisms may involve metformin’s previously described anti-inflammatory and anti-thrombotic effects,’ Shalev said. The study included 25 326 patients tested for COVID-19 at the tertiary care UAB Hospital between 25 February and 22 June of last year. Of the 604 patients found to be COVID-19-positive, 311 were African Americans. The primary outcome in the study was mortality in COVID-19-positive subjects, and the potential association with subject characteristics or co-morbidities was analysed. Researchers found that blacks, who are only 26% of Alabama’s population, were 52% of those who tested positive for COVID- 19, and only 30% of those who tested negative. In contrast, only 36% of the COVID-19-positive subjects were white, while whites made up 56% of those who tested negative, further underlining the racial disparity. Once COVID-19-positive though, no significant racial difference in mortality rate was observed. ‘In our cohort,’ Shalev said, ‘being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socio-economic factors, including access to proper healthcare.’ Overall mortality for COVID-19-positive patients was 11%. The study found that 93% of deaths occurred in subjects over the age of 50 years, and being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality rate, with an odds ratio of 3.62. Overall, 67% of deaths in the study occurred in subjects with diabetes. The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for type 2 diabetes. They found that prior insulin use did not affect mortality risk. However, prior metformin use was a different matter. Metformin use significantly reduced the odds of dying, and the 11% mortality rate for metformin users was not only comparable to that of the general COVID-19-positive population, it was dramatically lower than the 23%mortality rate for diabetes patients not on metformin. After controlling for other covariates, age, gender and metformin use emerged as independent factors affecting COVID-19-related mortality. Interestingly, even after controlling for all these other covariates, death was significantly less likely – with an odds ratio of 0.33 – for type 2 diabetes subjects taking metformin, compared with those who did not take metformin. ‘These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality,’ Shalev said, ‘this risk is dramatically reduced in subjects taking metformin – raising the possibility that metformin may provide a protective approach in this high-risk population.’ The researchers say future studies will need to explore how metformin is protective, as well as assess the risks and benefits of metformin treatment and the indications for its use in the face of the ongoing COVID-19 pandemic. 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