DPP4 inhibitors and COVID19 outcomes in patients with type II diabetes: a multicenter retrospective cohort study in Saudi Arabia

Dipeptidyl peptidase-4 inhibitors (DPP-4is) have been hypothesized to impact COVID-19 outcomes by modulating immune and inflammatory responses. This study aimed to assess the association between DPP-4i use and COVID-19 severity in patients with type 2 diabetes. Adult (≥ 18 years) patients with T2DM hospitalized for COVID-19 across seven hospitals in Saudi Arabia between March 2020 and November 2021 were included. Outcomes were in-hospital mortality, progression to mechanical ventilation (MV), intensive care unit (ICU) admission, and length of stay. We performed time-to-event analyses using Cox proportional hazards models with propensity score weighting to account for confounders. Ordinal proportional odds model were for the length of stay outcomes. A total of 166 patients were included in the DPP-4i group, and 351 were included in the non-DPP-4i group. Propensity score weighting achieved a well-balanced comparison between the groups. The DPP-4i group showed a nonsignificant decrease in mortality (adjusted hazard ratio [HRadj] = 0.73; 95% confidence interval [CI]: 0.40-1.34; p = 0.319), a significant reduction in progression to MV (HRadj = 0.40; 95% CI: 0.21-0.77; p = 0.006), and a nonsignificant reduction in ICU admissions (HRadj = 0.83; 95% CI: 0.57-1.21; p = 0.338). Length of stay did not differ significantly between groups. This study revealed that prior usage of DPP-4is in T2DM patients with COVID-19 is linked to a significant reduction in progression to MV in this high-risk group. However, there is a need for further investigation through well-powered prospective studies and randomized controlled trials to confirm these findings.