Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses. Glucose-regulating medications such as glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and pioglitazone are known to have anti-inflammatory effects that may improve outcomes in patients with SARS-CoV-2 infection. In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 56 large healthcare organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days following a COVID-19 diagnosis. After matching for age, sex, race, ethnicity, body mass index, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions (GLP-1R: 15.7% vs 23.5%; RR, 0.67 [95% CI, 0.57-0.79]; P <.001; pioglitazone: 20.0% vs 28.2%; RR, 0.71 [95% CI, 0.54-0.93]; P =.01). Use of GLP-1R agonists was also associated with reductions in respiratory complications (15.3% vs 24.9%; RR, 0.62 [95% CI, 0.52-0.73]; P <.001) and incidence of mortality (1.9% vs 3.3%; RR, 0.58 [95% CI, 0.35-0.97]; P =.04). Use of DPP-4 inhibitors was associated with a reduction in respiratory complications (24.0% vs 29.2%; RR, 0.82 [95% CI, 0.74-0.90]; P <.001), and continued use of DPP-4 inhibitors after hospitalization was associated with a decrease in mortality compared with those who discontinued use (9% vs 19%; RR, 0.45 [95% CI, 0.28-0.72]; P <.001). In conclusion, use of glucose-regulating medications such as GLP-1R agonists, DPP-4 inhibitors, or pioglitazone may improve outcomes for COVID-19 patients with T2DM; randomized clinical trials are needed to further investigate this possibility.