Association Between Dipeptidyl Peptidase-4 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists and COVID-19 Infection and Adverse Outcomes: a Cohort Study

Introduction People with type 2 diabetes (T2DM) have an elevated risk of adverse outcomes from COVID-19. Dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 receptor agonists (GLP1RAs) might have favorable effects on COVID-19 outcomes.Research design and methods We conducted a population-based cohort study in Ontario, Canada. We compared the risk of both COVID-19 infection as well as adverse outcomes between users of DPP4i or GLP1RA and users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or sulfonylureas (SUs). The study population was persons ≥66 years with T2DM taking metformin who had ≥1 COVID-19 PCR test between January 2020 and July 2021. We compared (1) COVID-19 infection and (2) adverse outcomes at 30 days among COVID-19 positive patients (major cardiovascular (CV) events, hospitalizations, intensive care unit admission, all-cause mortality, venous thromboembolism, mechanical ventilation). We reported weighted risk differences (RDs) and relative risks (RRs).Results There were 26,485 DPP4i/GLP1RA users (mean age 76, 47% female, 91% DPP4i users) and 14,487 SGLT2i/SU users (mean age 75, 39% female, 65% SGLT2i users). The weighted rate of COVID-19 infection in DPP4i/GLP1RA users was 10.3% compared with 10.4% among SGLT2i/SU users (weighted RD −0.06, 95% CI −0.79 to 0.66; RR 0.99, 95% CI 0.93 to 1.07). Among COVID-19 positive patients, the weighted RD for all-cause hospitalization for DPP4i/GLP1RA users versus SGLT2i/SU users was −6.72% (95% CI −3.02 to −10.4) and the adjusted weighted RR was 0.79 (95% CI 0.70 to 0.89). For major CV events, the weighted RD was −1.91% (95% CI −4.00 to 0.18) and RR 0.73 (95% CI 0.54 to 1.00).Conclusions DPP4i/GLP1RA use was not associated with reduced risk of COVID-19 infection compared with SGLT2i/SU use. DPP4i/GLP1RA use was associated with reduced risk of 30-day hospitalization among COVID-19 positive older adults and a possible trend towards a lower associated risk of CV events.