DPP-4 Inhibitors Lower COVID-19 Mortality in Patients With Type 2 Diabetes

blood glucose test and covid
person doing fingertip test for blood glucose, with vacuum tube for blood testing of test blood with covid-19 label
Investigators aimed to determine the association of pre-existing DPP-4is use with COVID-19–related outcomes among patients with T2DM.

Use of dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes mellitus (T2DM) who test positive for COVID-19 is independently associated with lower mortality in such patients, researchers reported in Diabetes Therapy.

The multicenter, retrospective study used data from the Turkish National Database to investigate the association of pre-existing DPP-4is use with COVID-19-related outcomes among patients with T2DM. Patients with T2DM who tested positive for COVID-19 with a polymerase chain reaction (PCR) test from March 11, 2020, to May 30, 2020, were screened for eligibility.

A total of 33,478 patients (median [interquartile range] age, 54 (22) years; 42.4% men) were included in the analysis; 6846 of these patients (20.5%) were taking DPP-4is. From the overall cohort, 4550 patients using DPP-4is and 4550 who were using other glucose-lowering drugs (n=4550) were matched in 2 groups. Participants in the DPP-4is group were significantly older, more frequently men, less frequently smokers, and received a lower level of education, compared with those in the non-DPP-4is group.

Among the patients who received DPP-4is, 9.5% died, vs 11.8% of patients who were using other glucose-lowering medications (P <.001).

Hospitalization occurred in 66.3% of patients receiving DPP-4is and in 65.7% of those who were using other glucose-lowering drugs (P =.595). DPP-4is use was associated with a significantly lower rate of intensive care unit admission and mechanical ventilation compared with other glucose-lowering drugs (21.7% vs 25.2%; P =.001).

In the overall cohort, multivariate regression analysis for mortality demonstrated that pre-existing use of DPP-4is (odds ratio [OR], 0.57; 95% CI, 0.35-0.91; P =.02) was independently associated with mortality, in addition to age (OR, 1.08; 95% CI, 1.05-1.10; P <.001), male sex (OR, 2.09; 95% CI, 1.37-3.19; P =.001), computed tomography finding of COVID-19 (OR, 1.60; 95% CI, 1.08-2.37; P =.019), obesity (OR, 1.87; 95% CI, 1.22-2.84; P =.004), chronic kidney disease (OR, 3.21; 95% CI, 1.55-6.65; P =.002), and use of insulin-based regimens (OR, 2.39; 95% CI, 1.51-3.80; P <.001).

The researchers noted a number of study limitations. The testing protocol for COVID-19 was not universal, and many mild cases may have been undetected. Additionally, some data were lacking, the potential effects of unmeasured confounding factors cannot be excluded, and no imputation was done during the analyses.

“The findings from this sizeable COVID-19 registry study indicate that pre-existing treatment with DPP-4is may be associated with a reduction in mortality in patients with T2DM,” stated the investigators. “The nearly 50% lower mortality observed in this group is also reassuring in terms of their safety during the COVID-19 pandemic,” they concluded.


Emral R, Haymana C, Demirci I, et al. Lower COVID-19 mortality in patients with type 2 diabetes mellitus taking dipeptidyl peptidase-4 inhibitors: results from a Turkish nationwide study. Diabetes Ther. Published online August 16, 2021. doi: 10.1007/s13300-021-01133-8