Metformin and Sulfonylurea Use in People With Type 2 Diabetes and COVID-19

Antidiabetic agents may increase pneumonia risk
Antidiabetic agents may increase pneumonia risk
COVID-19 can cause additional complications and even death in people with a pre-existing conditions like type 2 diabetes. Researchers studied whether the medications people with type 2 diabetes often take were associated with a risk of dying from the virus.

Antidiabetic agents such as metformin and sulfonylurea may reduce the risk of mortality in patients with type 2 diabetes (T2D) who contract COVID-19, while the use of insulin in these patients may be associated with a higher risk of mortality, according to research published in Frontiers in Endocrinology.

The research findings were based on a meta-analysis of 18 studies that consisted of a pooled cohort of 17,338 patients with T2D and concomitant COVID-19. All studies reported mortality outcomes.

Researchers who performed the meta-analysis assessed the relationship between mortality and the use of antidiabetic agents, including sulfonylurea, metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, α-glucosidase inhibitors, and/or insulin.

According to the investigators, there were significant associations between mortality and the antidiabetic agents metformin, sulfonylurea, and insulin (P <.05 for all). In contrast, there was no significant association between mortality and the use of DPP-4 inhibitors (P >.05).

In a pooled analysis of 14 studies on metformin, the researchers found a significantly lower mortality rate in patients treated with metformin vs those who weren’t (odds ratio [OR], 0.69; 95% CI, 0.55–0.86; P =.001). A pooled analysis of 5 studies focused on sulfonylurea use found a significant association between the use of sulfonylurea and lower mortality compared with nonuse (OR, 0.80; 95% CI, 0.66–0.96; P =.016).

There was no significant difference between users and nonusers of DPP-4 inhibitors in terms of mortality in 8 studies (OR, 0.72; 95% CI, 0.51–1.01; P =.057). Insulin users had significantly higher mortality than nonusers across 7 studies (pooled OR, 2.20; 95% CI, 1.34–3.60; P=.002).

The researchers noted that all the studies in the meta-analysis were observational in nature, so the study results are only hypothesis-generating. “Further larger trials should also be done to confirm these results and especially other diabetes drugs including SGLT2 inhibitors and DPP-4 inhibitors,” the researchers wrote.


Kan C, Zhang Y, Han F, et al. Mortality risk of antidiabetic agents for type 2 diabetes with COVID-19: a systematic review and meta-analysis. Front Endocrinol (Lausanne). Published online September 16, 2021. doi:10.3389/fendo.2021.708494