Association between Add-On Dipeptidyl Peptidase-4 Inhibitor Therapy and Diabetic Retinopathy Progression

This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged >= 40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of >= 80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research.