Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

Authors: Rifat Emral, Cem Haymana, Ibrahim Demirci, Ilker Tasci, Mustafa Sahin, Erman Cakal, Naim Ata, Ugur Unluturk, Tevfik Demir, Derun Ertugrul, Ibrahim Sahi, Aysegül Atmaca, Osman Celik, Murat Caglayan, Kazim Yalcin Arga, Selcuk Dagdelen, Serpil Salman, Ilhan Satman & Alper Sonmez

Abstract

Introduction

To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM).

Methods

A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population.

Results

A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35–0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39–1.08; p = 0.099).

Conclusions

The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.