Incretin-based therapies (IBTs) do not increase the risk for diabetic retinopathy in older adults with diabetes compared with alternative agents, according to findings published in Diabetes Care.

Recently conducted clinical trials have found conflicting results with regard to the association between IBT use and diabetic retinopathy in patients with diabetes. The current trial used an active comparator, new-user cohort design that compared IBTs with alternative therapies to see whether there was an association with a higher risk for diabetic retinopathy. The cohort was drawn from a random sample of fee-for-service US Medicare beneficiaries aged 65 years or older, and of this group, 213,652 eligible patients were identified.

Researchers compared the following groups of cohorts, none of whom had received prior treatment for retinopathy: dipeptidyl peptidase 4 inhibitors (DPP4i) vs sulfonylureas (SU), DPP4i vs thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP1RA) vs long-acting insulin (LAI), and GLP1RA vs TZD. The primary outcome was advanced diabetic retinopathy requiring treatment.

At a median duration of 0.58 to 0.87 years across all comparative groups, with a rate from 6.0 to 12.8 per 1000 person-years, IBTs were not associated with an increased risk for advanced diabetic retinopathy requiring treatment. The adjusted hazard ratios for advanced diabetic retinopathy requiring treatment were 0.91 (95% CI, 0.79-1.04) when comparing DPP4i with SU (n=39,292 and n=87,073), 0.91 (95% CI, 0.75-1.11) when comparing DPP4i with TZD (n=51,410 and n=22,231), 0.50 (95% CI, 0.39-0.65) when comparing GLP1RA with LAI (n=9561 and n=82,849), and 0.75 (95% CI, 0.53-1.06) when comparing GLP1RA with TZD (n=10,355 and n=27,345).

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The investigators note that they “only assessed short-term IBT use, as the real-world adherence is low.” Thus, the “short follow-up in this study may impair the potential for detecting differences with long-term use of these drugs,” they wrote.


Wang T, Hong JL, Gower EW, et al. Incretin-based therapies and diabetic retinopathy: real-world evidence in older U.S. adults [published online July 16, 2018]. Diabetes Care. doi: 10.2337/dc17-2285