Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study

Abstract

Objective: Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population.

Research design and methods: In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020.

Results: Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66]; P = 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P = 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P = 0.0008) compared with patients receiving standard of care, respectively.

Conclusions: In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

Figure 1

Mortality in patients with type 2 diabetes and COVID-19 treated with sitagliptin or receiving standard of care. A: Time to clinical end point (death/hospital discharge) in sitagliptin-treated patients and in the standard-of-care group. B: Bar graph representing mean blood glucose levels measured during the hospitalization in the two groups. Data are represented as mean ± SEM. No, number of patients.

Figure 2

Subgroup analysis in patients (pts) with type 2 diabetes and COVID-19 treated with sitagliptin or receiving standard of care. Forest plots of subgroup analyses exploring the effect of treatment with sitaliptin/standard of care in patients with type 2 diabetes and COVID-19. Subgroups include age (≥70 or <70 years), sex (males or females), baseline HbA_1c (>7.5% or ≤7.5%), and baseline BMI (>29 kg/m² or ≤29 kg/m²).