Do Some Diabetes Drugs Reduce the Risk of Severe or Fatal COVID-19?

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For patients with COVID-19, two newer classes of antihyperglycemic medications are associated with lower rates of death and other adverse outcomes, according to a study in Diabetes Care.

The observational study included 12,466 adult patients with polymerase chain reaction-diagnosed SARS-CoV-2 infection, drawn from the US National COVID Cohort Collective. Included patients had an ambulatory prescription for at least one of three antihyperglycemic medication classes over 24 months before diagnosis: glucagon-like peptide-1 receptor agonist (GLP1-RA), sodium-glucose cotransporter-2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP4i). The patients' mean age was 58.6 years, 53.4% were women, and 62.5% were White race.

Sixty-day mortality and other severe outcomes were compared for patients with premorbid GLP1-RA or SGLT2i use versus DPP4i use. Associations were analyzed with targeted maximum likelihood estimation (TMLE) using a super learner approach, accounting for baseline characteristics.

Patients taking DPP4i drugs were older and had a lower body mass index (BMI) compared to GLP1-RA or SGLT2i users. Patients in the DPP4i group were also more likely to have chronic or end-stage kidney disease, myocardial infarction, congestive heart failure, cancer, dementia, or stroke.

Crude 60-day mortality was 2.06% for patients with pre-morbid GLP1-RA use and 2.32% for those with SGLT2i use, compared to 5.67% for DPP4i users. Total mortality over the observation period was 2.29%, 2.48%, and 6.18%, respectively. In propensity score-weighted analyses, 60-day mortality was 2.31% in GLP1-RA users versus 4.86% in DPP4i users and 2.70% in SGLT2i users versus 4.74% in DPP4i users. Differences in total mortality also remained significant.

On TMLE analysis, odds ratio (OR) for 60-day mortality was 0.54 for GLP1-RA users versus DPP4i users. Secondary outcome ORs were 0.56 for total mortality, 0.81 for emergency department (ED) visits, 0.73 for hospitalization, and 0.73 for mechanical ventilation. For GLP1-RA versus DPP4i use, ORs were 0.66 for 60-day mortality, 0.63 for total mortality, 0.90 for ED visits, and 0.82 for hospitalization.

Patients with diabetes are at increased risk of death and other adverse outcomes of COVID-19. The newer antihyperglycemic medications GLP1-RA and SGLT2i have been shown to reduce cardiorenal events in high-risk groups. The new study explored the possible impact of these drug classes on COVID-19 outcomes.

The results show lower odds of mortality and other adverse events among COVID-19 patients with premorbid GLP1-RA and SGLT2i use, compared to those prescribed DPP4i medications. The authors note some important limitations of their study, including the older age and higher comorbidity of the DPP4i group. Anti-inflammatory effects of GLP1-RA and SGLT2i drugs might account for the associated improvement in COVID-19 outcomes [Kahkoska AR, et al. Association between glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor use and COVID-19 outcomes. Diabetes Care 2021; 44:1564–1572. doi: 10.2337/dc21-0065].