Diabetes Drug May Hold Potential as COVID-19 Treatment

In patients with type 2 diabetes (T2D) admitted to the hospital for coronavirus disease 2019 (COVID-19), treatment with sitagliptin was associated with reduced mortality and improved clinical outcomes compared with standard-of-care treatment, according to a study published in Diabetes Care. In addition, the underlying mechanism of sitagliptin leads researchers to hypothesize the drug may be effective in patients with COVID-19 and without T2D.

The CDC lists T2D as a preexisting factor that can put individuals at an increased risk of severe illness from COVID-19. In June, it was reported that patients with diabetes account for over 20% of individuals admitted to intensive care units for COVID-19.

Sitagliptin is an oral dipeptidyl peptidase 4 (DPP-4) inhibitor and recent studies have suggested that SARS-CoV-2, the virus that causes COVID-19, may bind DPP-4 when entering cells of the respiratory tract.

“Based on the modeling of SARS-CoV-2 structure and receptors, it has been also postulated that DPP-4 may facilitate the SARS-CoV-2 entry into target cells, due to its high homology with Middle East respiratory syndrome coronavirus,” authors wrote.

Researchers conducted a multicenter, case-control, retrospective observational study to investigate the effects of sitagliptin, a blood-sugar lowering drug, in patients with T2D and concurrent COVID-19.

A total of 338 consecutive patients admitted to 7 Northern Italy hospitals between March 1 and April 30, 2020 were included in the study. Patients treated with sitagliptin were matched in a 1:1 ratio with untreated control subjects. At admission, all participants had pneumonia and oxygen saturation <95% when breathing ambient air or were receiving oxygen support.

As standard of care, patients were switched at admission “from current treatment for T2D, which included mostly metformin, but also insulin, sulfonylureas, DPP-4 inhibitors, sodium–glucose cotransporter 2 inhibitors, GLP-1 receptor agonists, glinides, and thiazolidinediones, to insulin treatment (intravenously or subcutaneously).”

Overall, 169 patients received sitagliptin as an add-on therapy to standard care and 169 controls received only standard care. Mean age of those in both groups was 69 and no major demographic differences between the 2 groups were observed.

The study’s primary endpoints included discharge from the hospital, death, and improvement of clinical outcomes, measured by an increase of at least 2 points on a 7-category modified ordinal scale.

Analyses revealed treatment with sitagliptin, compared with patients receiving standard care, was associated with:

• Reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29–0.66]; P = .0001)
• An improvement in clinical outcomes (60% vs. 38% of improved patients; P =.0001)
• A greater number of hospital discharges (120 vs. 89 of discharged patients; P = .0008)
• A decreased risk for the need of mechanical ventilation (HR 0.27 [CI 0.11–0.62]; P = .003)
• Lower mean blood glucose levels measured during the hospitalization
• Lower mortality (29% vs. 51%) and better outcomes in a time to clinical end point analysis in patients aged 70 years or older

At day 30, a greater number of patients who received sitagliptin were discharged from the hospital compared with the control group. No treatment-related severe adverse events were reported in the intervention group.

Based on the findings, a new randomized, placebo-controlled trial of sitagliptin is now preparing to enroll patients with T2D in Europe.

Furthermore, “given the beneficial effects observed in lowering mortality rate and improving clinical outcomes, sitagliptin may also be considered for further testing in patients with COVID- 19 and without T2D,” authors wrote.

A randomized controlled trial to test the hypothesis is moving forward toward regulatory approval, according to a press release.

Reference:

Solerte SB, D’Addio F, Trevisan R, et al. 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. Diabetes Care. Published online September 29, 2020. doi:10.2337/dc20-1521