Sitagliptin confers survival benefit in COVID-19 patients with diabetes

Initiating COVID-19 patients with type 2 diabetes (T2D) on sitagliptin at the time of hospitalization appears to reduce mortality and improve clinical outcomes as compared with administering standard-of-care treatment alone, a study has found.

“Dipeptidyl peptidase-4 (DPP-4) inhibitors may be beneficial for COVID-19 in multiple aspects,” as pointed out by a team of Italy-based researchers.

For the most part, the drugs may prevent SARS-CoV-2–related detrimental effects as the binding site for the virus' spike protein S1 exhibits structural homology to the DPP-4 sequence. This suggests that sitagliptin may reduce SARS-CoV-2 virulence and prevent the ensuing multiorgan failure and acute and chronic injury to the lungs, as well as impede the cytokine storm caused by pulmonary damage, they explained. [Science 2020;367:1444-1448; Emerg Microbes Infect 2020;9:601-604]

DPP-4 inhibitors may also reduce the excessive and prolonged cytokine responses observed in COVID-19 patients by modulating DPP-4 expression on immune cells, they added. “[Finally], sitagliptin may improve glycometabolic control, which would likely [antagonize] the clinical progression of COVID-19,” according to the researchers. [Emerg Microbes Infect 2020;9:601-604; Eur J Pharm Sci 2017;100:17-24; Cell Metab 2020;31:1068–1077.e3; Diabetes Care 2020;43:1399-1407]

In the present study, the researchers looked at 338 consecutive patients (mean age, 69 years; 70.4 percent male) with T2D and COVID-19 admitted in Northern Italy. Half of the population received standard of care alone, while the other half were given add-on sitagliptin.

Indeed, more patients died in the standard-of-care group (37 percent vs 18 percent). On multivariable Cox analysis, sitagliptin produced a 66-percent reduction in the risk of mortality (hazard ratio, 0.44, 95 percent confidence interval, 0.29–0.66; p=0.0001). [Diabetes Care 2020;10.2337/dc20-1521]

In parallel, significantly more patients who received the DPP-4 inhibitor exhibited improved clinical outcomes (60 percent vs 38 percent; p=0.0001) and were discharged from the hospital at day 30 (120 vs 89 patients; p=0.0008).

Preadmission therapy with metformin, insulin, or other glucose-lowering agents did not influence clinical outcomes.

Regardless of the presence of several limitations, the study indicates that T2D patients hospitalized for COVID-19 may fare well with the addition of sitagliptin to standard of care, according to the researchers.

The benefits of sitagliptin in diabetic patients with COVID-19 should be confirmed in a randomized, placebo-controlled trial with extended primary and secondary endpoints, including the measurement of DPP-4 level in biological samples collected at multiple time points, as well as tested in patients without diabetes, they added.