DPP-4 Inhibitor Tied to Lower Mortality in T2D Patients With COVID-19

Among hospitalized COVID-19 patients with type 2 diabetes, sitagliptin (Januvia) treatment was linked with lower in-hospital mortality, researchers reported.

In a retrospective study of 338 patients admitted in Northern Italy, those who were given the dipeptidyl peptidase 4 (DPP-4) inhibitor on top of standard of care insulin at the time of hospitalization saw significantly lower odds of in-hospital death versus those on standard of care alone (odds ratio 0.37, 95% CI 0.23-0.62, P=0.0001), according to Paolo Fiorina, MD, PhD, of Boston Children's Hospital, and colleagues.

This equated to an 18% mortality rate among COVID-19 patients with type 2 diabetes on sitagliptin versus a 37% mortality rate among those on standard of care, they wrote in Diabetes Care.

Treatment with sitagliptin also was tied to a significantly reduced need for mechanical ventilation (HR 0.27, 95% CI 0.11-0.62, P=0.003), and a 49% reduced risk for needing intensive care while in the hospital versus patients treated with standard of care (HR 0.51 95% CI 0.27-0.95, P=0.03).

Additionally, patients on sitagliptin saw a greater extent of clinical improvement, as measured by a two-point reduction or greater on the seven-point category scale at day 30 of follow-up. Overall, 52% of patients on sitagliptin saw this amount of clinical improvement versus only 34% of those on standard of care.

Out of 169 patients, 120 on sitagliptin were discharged from the hospital after 30 days versus 89 on standard of care (P=0.0008).

However, there wasn't any difference between the groups in the requirement of extracorporeal membrane oxygenation (HR 1.15, 95% CI 0.41-3.17, P=0.77).

"We think it's reasonable to try sitagliptin if a patient is admitted to the hospital with type 2 diabetes and COVID," Fiorina said in a statement. "I'm excited about our findings, because we still have very few therapeutic options for the many diabetic patients affected by COVID."

The authors evaluated data from seven hospitals in Northern Italy during the first wave of the COVID-19 pandemic from March 1 through April 30, 2020. All patients (mean age 69; majority male) had pre-existing type 2 diabetes and were admitted with pneumonia. They had an oxygen saturation below 95% when breathing ambient air or when on oxygen support.

Upon admission, all patients were switched to standard of care, which was IV or subcutaneous insulin administered according to the modified Yale insulin protocol, with a glycemic target between 140 to 180 mg/dL. Among the half of patients who were given sitagliptin in addition to insulin, sitagliptin was then given at a dose adjusted for eGFR level: 100 mg once daily if eGFR was 45 mL/min/1.73 m² or above or only 50 mg if eGFR was below 45. The two groups were matched for both age and sex.

No other glucose-lowering agents were administered during this time.

The researchers pointed out several potential mechanisms of action that may have led to these outcomes. In addition to improving glycemic control from blocking DPP-4, sitagliptin also had anti-inflammatory and immunoregulatory properties. This included an inhibition in cytokine IL-6 production, reducing the potential for a cytokine storm.

"We must now confirm our findings in a placebo-controlled, prospective study," Fiorina noted, adding that his group also hopes to test the effects of sitagliptin in COVID-19 patients who are free of diabetes.

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