FDA-Approved Drug to Lower Blood Sugar Nearly Halves Mortality in Diabetic Patients Hospitalized With COVID-19

A multicenter observational study has found that an FDA-approved drug to lower blood sugar in Type 2 diabetes also cuts mortality in diabetic patients hospitalized with COVID-19 by as much as half.

In 2006, the Food and Drug Administration had approved the drug sitagliptin to lower blood sugar in Type 2 diabetes. In a study led by Boston Children’s Hospital (Boston, MA, USA) that involved seven Italian hospitals during the first surge of COVID-19 cases last spring, researchers found that patients who received sitagliptin in addition to insulin had a mortality rate of 18%, as compared with 37% in matched patients receiving only insulin.

Sitagliptin belongs to a class of drugs known as DPP-4 inhibitors, which are prescribed to an estimated 15 to 20% of patients with Type 2 diabetes. The drug lowers blood sugar by blocking the receptor for the enzyme DPP-4 (also called CD26), which increases production of insulin. But recent studies suggest that DPP-4 has two side actions that are relevant to COVID-19. It may help the SARS-CoV-2 coronavirus get into respiratory cells. It also curbs inflammation, reducing production of the cytokine IL-6 that contributes to the “cytokine storm” causing organ complications in COVID-19. Sitagliptin’s main action, lowering blood sugar, may also help boost survival. Previous studies have shown that diabetic patients with worse glycemic control have worse COVID-19 outcomes.

The study enrolled 338 consecutive patients with Type 2 diabetes and COVID-19 pneumonia who were admitted to seven academic hospitals in northern Italy in March and April. Of these, 169 received only IV insulin for their Type 2 diabetes (the standard of care) and served as controls; the other 169 also received sitagliptin. The researchers matched the two groups for age and sex, and reviewed their outcomes retrospectively. Illness severity, other clinical characteristics, and use of other treatments for COVID-19 were similar in the two groups. In addition to increased survival, patients treated with sitagliptin were less likely than controls to need mechanical ventilation; less likely to need intensive care; more likely than controls to have at least a 2-point drop on a 7-point scale of disease severity; and less likely to have a worsening of clinical outcomes, as defined by any increase in the clinical severity score.

Based on sitagliptin’s mechanism of action, the researchers believe that it could also help fight COVID-19 even in non-diabetic patients. Although the study was retrospective and observational, the findings have sparked a new randomized, placebo-controlled trial of sitagliptin. The separate randomized, controlled trial to test that idea is moving toward regulatory approval and is now preparing to enroll patients in Europe.

“We think it’s reasonable to try sitagliptin if a patient is admitted to the hospital with Type 2 diabetes and COVID-19,” said Paolo Fiorina, MD, PhD, a diabetes researcher affiliated with Boston Children’s division of nephrology and the University of Milan, who led the study. “I’m excited about our findings, because we still have very few therapeutic options for the many diabetic patients affected by COVID-19.”

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Boston Children’s Hospital