Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis

Abstract

Introduction This systematic review and meta-analysis aimed to synthesize the latest evidence on the effect of dipeptidyl peptidase-4 (DPP-IV) inhibitor in patients with COVID-19. Methods We performed a systematic literature search from the PubMed, Scopus, Embase, and Clinicaltrials.gov up until 15 July 2021. Studies that met the following criteria were included: prospective or retrospective observational studies or case series or randomized controlled trials (RCTs) reporting DPP-IV inhibitor use in patients with COVID-19 and mortality. The intervention group was patients receiving DPP-IV inhibitor. The control group was patients that did not receive DPP-IV inhibitor. The outcome was mortality reported as odds ratio (OR). Results There were 11 studies consisting of 5,950 patients in this meta-analysis. DPP-IV inhibitor use was associated with reduced mortality (OR 0.75 [0.56, 0.99], p = 0.043, I 2 : 42.9, p = 0.064) compared to those that did not receive DPP-IV inhibitor. Sensitivity analysis using the fixed-effect model (OR 0.75 [0.63, 0.88], p < 0.001, I 2 : 42.9, p = 0.064) also showed mortality benefit. The association between DPP-IV inhibitor and mortality was not significantly affected by age (p = 0.540), sex (p = 0.054), hypertension (p = 0.320), location (continent; p = 0.532), and retrospective/prospective nature of the study (p = 0.840). However, the association was affected by metformin (OR 1.03 [95% CI 1.01, 1.06], p = 0.010) and ACEI/ARB use (OR 1.06 [95% CI 1.02, 1.10], p = 0.004). Conclusion This meta-analysis showed that DPP-IV inhibitor was associated with reduced mortality in patients with COVID-19.

Association of anti-diabetic drugs and COVID-19 outcomes in patients with diabetes mellitus type 2 and cardiomyopathy

“…In literature, DPP-4 inhibitors show mixed results regarding the association with COVID-19 death and hospitalization in diabetes mellitus patients. Meta-analyses found an association with mortality reduction 21 , 32 . However, another meta-analysis found DPP-4 inhibitors use was associated with almost 1.5 times higher hospitalization risk and increased risk of ICU admissions and/or mechanical ventilation vs. nonusers 30 .…”

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

“…Moreover, a prospective study with 89 COVID-19 but non-diabetic patients demonstrated that sitagliptin improved clinical outcomes, radiological scores, and inflammatory biomarkers, pointing to a potential usefulness of DPP4 inhibitors in managing non-diabetic COVID-19 patients [ 143 ]. A meta-analysis showed that the effect of gliptins was independent of age, sex, race, and location [ 144 ].…”

The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study

“…Notably, the use of sitagliptin was also associated with a reduced risk of mechanical ventilation and admission to intensive care units (ICUs), with Hazard Ratios (HRs) of 0.27 and 0.51, respectively [ 23 ]. In addition to these data and always in the context of COVID-19 inpatients, a multination meta-analysis showed that DPP-4is administration was associated with significantly reduced overall mortality rates (OR 0.75) [ 24 ].…”