Diabetes and COVID-19: What have we learned so far?

Evidence for excess risk and increased burden of new-onset diabetes among COVID-19 survivors is robust, and most antihyperglycaemic drugs can be used safely during acute COVID-19, with some drugs potentially offering protection against serious complications, according to data presented at 5^th EDM HK.

The notion that COVID-19 may induce diabetes came from observations of hyperglycaemic emergencies (ie, diabetic ketoacidosis and/or hyperosmolar hyperglycaemic state) in patients hospitalized with COVID-19. [Lancet Diabetes Endocrinol 2020;8:660-663]

In a cohort study using data from national databases of the US Department of Veterans Affairs, 181,280 participants (mean age, 60.92 years; male, 88.08 percent) who tested positive for COVID-19 and survived the first 30 days thereafter were included. Individuals with COVID-19 showed an increased risk (hazard ratio [HR], 1.46; 95 percent confidence interval [CI], 1.43–1.50) and excess burden (18.03 per 1,000 individuals at 12 months; 95 percent CI, 16.59–19.51) of incident diabetes or use of antihyperglycaemic drugs vs controls. [Lancet Diabetes Endocrinol 2022;10:311-321]

“Based on results of the cohort study, we would be picking up another 36,000 new cases of diabetes [in Hong Kong],” estimated Professor Andrea Luk of the Department of Medicine & Therapeutics, Chinese University of Hong Kong (CUHK).

“The mechanism for new-onset diabetes [in COVID-19 survivors] is not well understood. It is likely to be a complex and interrelated process including stress-induced insulin resistance, drug-induced hyperglycaemia, lifestyle changes during the pandemic, induction of autoimmunity and pancreatic beta cell dysfunction,” explained Luk.

To investigate the association between baseline use of antihyperglycaemic drugs and serious adverse outcomes from COVID-19 among Chinese patients with type 2 diabetes (T2D), Luk and colleagues at CUHK conducted a population-wide retrospective study that included 1,220 patients with T2D admitted for confirmed COVID-19 (mean age, 65.3 years; male, 54.3 percent) between January 2020 and February 2021 in Hong Kong. Use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors was associated with a significantly reduced risk of the composite endpoint of intensive care unit admission, mechanical ventilation and/or in-hospital death vs nonuse of these medications (metformin: HR, 0.51; p=0.001) (DPP-4 inhibitors: HR, 0.46; p<0.001). However, insulin and sulphonylureas were associated with an increased risk of the composite endpoint (insulin: HR, 6.34; p<0.001) (sulphonylureas: HR 1.55; p=0.022). [BMJ Open 2021;11:e052310]

Although the data are from Chinese patients and cannot be generalized to other ethnic groups, similar results were reported in other international trials in the US, UK and France. [Lancet Diabetes Endocrinol 2021;9:293-303; Diabetes 2021;70:2903-2916; Diabetologia 2021;64:778-794]

In the randomized, double-blind, phase III DARE-19 trial, 1,250 hospitalized COVID-19 patients with ≥1 cardiometabolic risk factor (mean age, 61.4 years; female, 42.6 percent) were randomized 1:1 to receive dapagliflozin or placebo for 30 days. Treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or a significant improvement in clinical recovery, but was well tolerated. [Lancet Diabetes Endocrinol 2021;9:586-594]

“These findings collectively indicate that many glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors, can be used safely and do not aggravate the disease course of acute COVID-19,” highlighted Luk. “There is no reason to prematurely discontinued these therapies in most situations, except in critically ill patients.”