COVID-19 patients taking the DPP-4 inhibitor sitagliptin had lower risk of needing intensive care or needing mechanical ventilation.
Type 2 diabetes has been associated with worse outcomes and an increased risk of mortality in patients with COVID-19, though it is not associated with increased susceptibility to the virus. It is known that SARS-CoV-2 enters host cells through the ACE2 receptor, but new data suggest that the virus may also bind DPP-4 when entering cells in the respiratory tract; thus, DPP-4 could play a role in the virulence of the virus. It has been suggested that inhibiting DPP-4 could provide benefit to patients infected with COVID-19. Sitagliptin is a highly selective DPP-4 inhibitor that has also shown anti-inflammatory and immunoregulatory effects. This study aimed to assess whether sitagliptin could help treat hospitalized COVID patients with type 2 diabetes.
This retrospective, case-control, observational study, conducted in Northern Italy, analyzed the data of type 2 diabetes patients hospitalized with COVID-19 between March 1 and April 30, 2020. The primary endpoints of the study were improvement of clinical outcomes, hospital discharge, or death. Improvement of clinical outcomes was defined as a ≥ 2-point reduction at day 30 of follow-up according to a modified seven-point category scale. The secondary endpoints included the need for intensive care, mechanical ventilation of ECMO. To be included in this study, patients had to have a type 2 diabetes diagnosis, a laboratory-confirmed SARS-CoV-2 infection, near-normal hepatic function (≤ a four-fold increase in aminotransferases levels), and an eGFR ≥ 30 mL/min/1.73m2.
The two groups observed in this study were the control group, which received the standard of care, insulin, or the sitagliptin group, which received both insulin and sitagliptin. Upon hospital admission, all antihyperglycemic medication was discontinued. Patients were either placed on the standard of care, with or without the addition of sitagliptin. The choice to add on DPP-4 inhibitors upon admission was decided by the treating physician, based on the patient’s clinical assessment and literature released from the pandemic areas. Patients were matched 1:1 between the groups for age and sex. Doses of sitagliptin were adjusted according to eGFR: 100 mg daily if eGFR ≥ 45 or 50mg if eGFR 30-45. The glycemic goal was 140-180 mg/dL and was assessed by obtaining an FBG and three blood glucose levels daily. Insulin was held if the BG dropped to ≤100 mg/dL.
Three hundred thirty-eight patients were included in this study: 169 patients in each group. 31 patients (18%) in the sitagliptin group died instead of 63 patients in the control group (p=0.0001). The odds of in-hospital death were 63% lower in the sitagliptin group (OR 0.37; 95% CI 0.23 – 0.62; p = 0.0001). Data on clinical improvement based on the modified seven-point category scale was only available in 139 patients taking sitagliptin and 145 patients solely taking insulin. 52% of patients taking sitagliptin had a ≥ 2 point improvement in clinical outcomes instead of 34% of patients taking insulin (p = 0.0005). The clinical endpoint showed patients taking sitagliptin had better clinical outcomes (HR 0.44; 95% CI 0.29 – 0.66). It also revealed that better outcomes were associated with better glycemic control.
Patients taking sitagliptin had a lower risk of needing intensive care (HR 0.51; 95% CI 0.27 – 0.95) and a substantially lower risk of needing mechanical ventilation (HR 0.27; 95% CI 0.11 – 0.62) than patients taking insulin alone. The need for ECMO was not significantly different between the two groups. Reductions in inflammatory marks such as CRP and procalcitonin were seen in the sitagliptin group. In subgroup analysis, better outcomes were associated with patients taking sitagliptin based on BMI even below 29 kg/m2 (p = 0.03) and in patients with an A1c > 7.5% (p = 0.0003).
This study found that sitagliptin use was associated with reduced mortality and improved clinical outcomes in type 2 diabetes patients hospitalized with COVID-19. These results suggest the DPP-4 inhibitors could have benefits for use in COVID-19 patients, including potential immunoregulatory effects, anti-inflammatory effects, and reduced virulence of SARS-CoV-2. Further testing, such as RCTs, could be performed to confirm these associations seen with sitagliptin.
- The odds of in-hospital death were 63% lower in patients taking sitagliptin and insulin vs. insulin alone.
- Patients taking sitagliptin were at a 49% lower risk of needing intensive care and a 73% lower risk of requiring mechanical ventilation.
- DPP-4 inhibitors could have benefits for use in COVID-19 patients, including potential immunoregulatory effects, anti-inflammatory effects, and reduced virulence of SARS-CoV-2.
Gheblawi, Mahmoud et al. “Angiotensin-Converting Enzyme 2: SARS-Cov-2 Receptor And Regulator Of The Renin-Angiotensin System”. Circulation Research, vol 126, no. 10, 2020, pp. 1456-1474. Ovid Technologies
Solerte, Sebastiano Bruno et al. “Sitagliptin Treatment At The Time Of Hospitalization Was Associated With Reduced Mortality In Patients With Type 2 Diabetes And COVID-19: Diabetes Care, 2020, p. dc201521.
Destiny Reed, PharmD. Candidate, Florida A&M College of Pharmacy and Pharmaceutical Sciences