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Disclosures: The authors report no relevant financial disclosures.
October 01, 2020
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Sitagliptin linked to lower mortality rate in adults with type 2 diabetes, COVID-19

Source/Disclosures
Disclosures: The authors report no relevant financial disclosures.
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Adults with type 2 diabetes who were hospitalized with COVID-19 in northern Italy had a lower mortality rate and better health outcomes when treated with the DPP-IV inhibitor sitagliptin, according to study data published in Diabetes Care.

Type 2 diabetes increases the mortality risk in patients with COVID-19, particularly in those with more severe disease,” Sebastiano Bruno Solerte, MD, associate professor and director of the geriatric and diabetology unit in the department of internal medicine at the University of Pavia, Italy, and colleagues wrote. “In patients with type 2 diabetes and COVID-19, poorly controlled blood glucose levels are associated with markedly higher mortality as compared with subjects with better metabolic control. Therefore, we examined whether sitagliptin, the DPP-IV inhibitor with higher selectivity for dipeptidyl-peptidase IV, may be beneficial in treating COVID-19, particularly in patients with type 2 diabetes who appear to be at high risk of mortality and of cardiorenal or cerebrovascular complications.”

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Researchers conducted an observational study of 338 adults with type 2 diabetes (mean age, 69 years) who were hospitalized for COVID-19 in one of seven academic medical centers in northern Italy between March 1 and April 30. Half of the participants were treated with sitagliptin (Januvia, Merck) administered at an adjusted dosage based on the person’s estimated glomerular filtration rate, whereas the other half received IV or subcutaneous insulin as standard of care. The groups were matched for age and sex, with no significant demographic differences between the two. Researchers analyzed the number of deaths and hospital discharges in each group, as well as the number of individuals who saw clinical improvement.

Individuals in the sitagliptin group had a lower likelihood of in-hospital mortality than those in the standard of care group (OR = 0.37; 95% CI, 0.23-0.62). The OR was unchanged after adjusting for age, sex, comorbidities and ongoing treatment. An analysis of time to death or hospital discharge also showed those receiving sitagliptin had better health outcomes than the standard of care group (HR = 0.44; 95%, 0.29-0.66). The sitagliptin group also had a decreased risk for use of a mechanical ventilator during hospitalization (HR = 0.27; 95% CI, 0.11-0.62) and ICU admission (HR = 0.51; 95% CI, 0.27-0.95) compared with people receiving standard of care.

Of 139 individuals in the sitagliptin group and 145 in the standard of care group for whom 30-day follow-up analysis of clinical improvement was conducted, 52% of the sitagliptin group showed improvement while 26% had a worse condition. In the standard of care group, 34% reported improved health while 46% had a worsening of clinical outcomes. At day 30, 120 people in the sitagliptin group had been discharged from the hospital compared with 89 in the standard of care cohort (P = .0008).

“DPP-IV inhibitors may be beneficial for COVID-19 in multiple aspects,” the researchers wrote. “First, sitagliptin may prevent SARS-CoV-2-related detrimental effects as the binding site for SARS-CoV-2 spike protein S1 identified through cryoelectron microscopy structure analysis of ACE2 has high homology with the DPP-IV sequence, thus suggesting that DPP-IV may facilitate SARS-CoV-2 entry into cells. Secondly, modulation of DPP-IV expression on immune cells by sitagliptin may induce broad anti-inflammatory and immunoregulatory effects. Thirdly and lastly, sitagliptin may improve glycometabolic control, which would likely benefit antagonism of the clinical progression of COVID-19.”

Researchers said the effects of sitagliptin in people with type 2 diabetes and COVID-19 should be further researched in a randomized, placebo-controlled trial.