Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Incident Diabetic Retinopathy

Diabetes Care. 2018 Nov;41(11):2330-2338. doi: 10.2337/dc17-2280. Epub 2018 Aug 27.

Abstract

Objective: Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy.

Research design and methods: Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis, new users of GLP-1 RAs were compared with new users of insulin.

Results: During 245,825 person-years of follow-up, 10,763 patients were newly diagnosed with diabetic retinopathy. Compared with current use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy overall (HR 1.00, 95% CI 0.85-1.17). Compared with insulin, GLP-1 RAs were associated with a decreased risk of diabetic retinopathy (HR 0.67, 95% CI 0.51-0.90).

Conclusions: The associations with diabetic retinopathy varied according to the type of comparator. When compared with use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy. The apparent lower risk of diabetic retinopathy associated with GLP-1 RAs compared with insulin may be due to residual confounding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Retinopathy / chemically induced*
  • Diabetic Retinopathy / epidemiology
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents

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