Incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta-analysis of observational studies

Diabetes Obes Metab. 2024 Feb;26(2):721-731. doi: 10.1111/dom.15367. Epub 2023 Nov 29.

Abstract

Aim: The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes.

Materials and methods: We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest. Risk of bias was assessed using the ROBINS-I tool. Data from included studies were pooled using the DerSimonian and Laird random-effect model with the Hartung-Knapp extension.

Results: We included 14 studies in the systematic review, with 10 examining DPP-4 inhibitors and seven examining GLP-1 RAs. Nine studies investigated incident diabetic retinopathy, six investigated diabetic retinopathy progression and two investigated both outcomes. Seven studies were at moderate risk of bias, four at serious risk of bias and three at critical risk of bias. Data pooled across studies showed no association between the use of DPP-4 inhibitors (risk ratio: 0.98, 95% confidence interval: 0.83, 1.17) or GLP-1 RAs (risk ratio: 0.87, 95% confidence interval: 0.56, 1.34) and the risk of diabetic retinopathy.

Conclusion: This study suggests that the use of incretin-based drugs is not associated with the risk of diabetic retinopathy among individuals with type 2 diabetes. However, these findings should be interpreted with caution considering the limited quality of some of the available evidence.

Keywords: diabetic retinopathy; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide 1 receptor agonists; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Retinopathy* / epidemiology
  • Diabetic Retinopathy* / etiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Incretins / adverse effects
  • Observational Studies as Topic

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins