Diabetes Metab J.  2019 Oct;43(5):640-648. 10.4093/dmj.2018.0137.

Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study

  • 1Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea. kie114@ajou.ac.kr
  • 2Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea. djkim@ajou.ac.kr
  • 3Department of Cardiovascular and Metabolic Disease Etiology Research Center, Ajou University School of Medicine, Suwon, Korea.
  • 4Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.


To investigate the effects of dipeptidyl peptidase-4 inhibitor (DPP4i) as add-on medications to metformin on progression of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus, compared with sulfonylurea (SU) or thiazolidinedione (TZD).
We identified 4,447 patients with DPP4i, 6,136 with SU, and 617 with TZD in addition to metformin therapy from the database of Korean National Health Insurance Service between January 2013 and December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for DR progression. The progression of DR was defined by the procedure code of panretinal photocoagulation, intravitreal injection or vitrectomy; or the addition of diagnostic code of vitreous hemorrhage, retinal detachment, or neovascular glaucoma.
The age and sex-adjusted HR of DR progression was 0.74 for DPP4i add-on group compared with SU add-on group (95% confidence interval [CI], 0.62 to 0.89). This lower risk of DR progression remained significant after additional adjustments for comorbidities, duration of metformin therapy, intravitreal injections and calendar index year (HR, 0.80; 95% CI, 0.66 to 0.97).
This population-based cohort study showed that the use of DPP4i as add-on therapy to metformin did not increase the risk of DR progression compared to SU.


Diabetes mellitus, type 2; Diabetic retinopathy; Dipeptidyl-peptidase IV inhibitors

MeSH Terms

Cohort Studies*
Diabetes Mellitus, Type 2
Diabetic Retinopathy*
Dipeptidyl-Peptidase IV Inhibitors
Glaucoma, Neovascular
Hypoglycemic Agents*
Intravitreal Injections
Light Coagulation
National Health Programs
Retinal Detachment
Vitreous Hemorrhage
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
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