Study Finds Small Association Between Type 2 Diabetes Drugs and COVID-19-Related Mortality

Male nurse checking hospitalized female diabetic patient while both wearing protective face masks – Pandemic lifestyles
The researchers investigated whether there are associations between different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes.

A study has found a small association between some glucose-lowering drugs and an increased risk of mortality associated with COVID-19 in patients with type 2 diabetes (T2D). The investigators believe the findings do not indicate patients with diabetes need to change their prescriptions because glucose control represents a key modifiable risk factor for COVID-19-related outcomes. Findings from this study were published in The Lancet Diabetes & Endocrinology.

This observational cohort study used data obtained from the National Diabetes Audit for people with T2D registered with a general practice in the UK. The investigators analyzed the rate of COVID-19-related mortality in patients who were prescribed glucose-lowering medications.

In total, the cohort study included 2,851,465 patients with T2D. Among these, 13,479 (0.5%) patients died because of COVID-19 between February and August 2020. The rate of COVID-19-related mortality in these patients with T2D was 8.9 per 1000 person-years (95% CI, 8.7-9.0).

The adjusted hazard ratios (HRs) associated with COVID-19-related death were 0.77 (95% CI, 0.73-0.81) in patients prescribed metformin and 1.42 (95% CI, 1.35-1.49) in patients prescribed insulin.

In addition, adjusted HRs for other glucose-lowering medications were 0.75 (95% CI, 0.48-1.17) for meglitinides, 0.82 (95% CI, 0.74-0.91) for SGLT2 inhibitors, 0.94 (95% CI, 0.82-1.07) for thiazolidinediones, 0.94 (95% CI, 0.89-0.99) for sulfonylureas, 0.94 (95% CI, 0.83-1.07) for GLP-1 receptor agonists, 1.07 (95% CI, 1.01-1.13) for DPP-4 inhibitors, and 1.26 (95% CI, 0.76-2.09) for α-glucosidase inhibitors.

A limitation of the study included the lack of data on medication adherence, resulting in potential ambiguity regarding the association between T2D drugs and COVID-19-related mortality risk.

Additionally, the investigators note that the lower risk of COVID-19-related mortality with sulfonylureas and SGLT2 inhibitors and higher risk with DPP-4 inhibitors in this study are likely due to residual confounding rather than the drugs’ effects.

The researchers concluded that there is currently a need for “studies to validate these findings in large national datasets in other countries.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Khunti K, Knighton P, Zaccardi F, et al. Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England. Lancet Diabetes Endocrinol. 2021;9(5):293-303. doi:10.1016/S2213-8587(21)00050-4