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

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 5950 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.