Linagliptin Does Not Reduce COVID-19 Recovery Time in Type 2 Diabetes

doctor speaking to patient in ICU wearing mask
Female doctor in protective suit consoling senior patient. Elderly man with oxygen mask is lying on bed in intensive care unit during COVID-19 crisis. They are in hospital ward.
Investigators compared linagliptin with standard of care treatment for clinical outcomes in people with type 2 diabetes who were hospitalized with COVID-19.

Linagliptin (Trajenta) did not reduce time to clinical improvement in patients with type 2 diabetes (T2D) who were hospitalized with COVID-19. These findings, from an open-label, prospective, multicenter randomized trial, were published in Frontiers in Endocrinology.

Between October 2020 and April 2021, patients (N=64) with T2D and COVID-19 infection were recruited for this study from 3 hospitals in Israel. Patients were stratified in a 1:1 ratio to receive 5 mg daily of linagliptin plus standard of care (n=32) or standard of care alone (n=32). The primary outcome was clinical improvement within 28 days of randomization, as defined by a 2-point reduction in the patient’s hospital admission status on a 9-point ordinal scale.

Patients were aged mean 66.95±13.93 years, 59.4% were men, median BMI was 29.1 (interquartile range [IQR], 26.6-33.3) kg/m2, 64.06% were receiving oxygen support on admission, diabetes duration was 13.5 (IQR, 8-19) years, and glycated hemoglobin (HbA1C) was 7.5% (IQR, 6.7%-8.8%). The intervention and control cohorts were well balanced with the exception that patients randomized to receive linagliptin had significantly lower HbA1C at admission (median, 7.4% vs 8.2%; P =.02).

Clinical improvement by day 28 was achieved by 81.3% in the linagliptin group and 71.9% of the standard of care only recipients (odds ratio [OR], 0.59; 95% CI, 0.18-1.91). The median time to improvement was similar between groups (median, 7 vs 8 days; hazard ratio [HR], 1.22; 95% CI, 0.70-2.15; P =.49).

A total of 7 patients in the linagliptin group and 4 patients in the control group were admitted to the intensive care unit (ICU) (OR:1.96, 95% CI, 0.51-7.50). All-cause mortality at 28 days was 7 (21.9%) and 9 (28.1%) in the linagliptin and standard of care groups, respectively.  The median length of hospitalization was 7 days in both groups (mean difference, 0.44; 95% CI, -2.83 to 3.71).

Each cohort had 1 hypoglycemia event. One patient who received linagliptin remained hospitalized in the ICU at day 28.

This study was limited by the low sample size; however, the study was terminated when the COVID-19 outbreak ended in Israel during the study.

“The administration of linagliptin in patients with COVID-19 and diabetes did not improve the time to clinical improvement or 28-day mortality,” the study researchers concluded.


Abuhasira R, Ayalon-Dangur I, Zaslavsky N, et al. A randomized clinical trial of linagliptin vs standard of care in patients hospitalized with diabetes and COVID-19. Front Endocrinol. 2021;12:794382. doi:10.3389/fendo.2021.794382