A new study published in Diabetes Care has shown that GLP-1 agonists do not pose an increased risk for diabetic retinopathy compared to other glucose-lowering agents; findings compare treatment with patients taking two or more glucose-lowering agents.
GLP-1 agonists are a unique, injectable class of glucose-lowering agents mimicking the effects of the incretin hormone GLP-1, which is released in response to carbohydrate intake. This class of medication controls type 2 diabetes by increasing insulin secretion from the pancreas, decreasing glucagon, and slowing gastric emptying, which in turn allows for weight loss and improved beta cell function in addition to managed blood glucose. While these agents are highly effective at controlling a patients’ diabetes, past studies have proposed that GLP-1 agonists may be linked to increased incidence of diabetic retinopathy as compared to other glucose-lowering agents.
Diabetic retinopathy affects around one third of patients with diabetes and, as of 2015, is the leading cause of vision loss around the world. While unmanaged high blood glucose levels are often the main culprit for this hindering complication, could certain medications also be a contributor?
Investigators in this new study sought to answer this question, conducting a cohort of over 70,000 patients with type 2 diabetes in the U.K Clinical Practice Research Datalink. All patients with type 2 diabetes 18 years and older, and initiating or changing an oral antidiabetic therapy were included in the analysis if they had enrolled in therapy between 2007 and 2015. Primary analysis was a comparison of GLP-1 agonists and oral glucose-lowering agents in their risk for diabetic retinopathy. Secondary analysis included GLP-1 agonists and insulin in their risk for diabetic retinopathy. Any patients with retinal disease, medical conditions associated with retinopathy, or those taking any medications associated with retinopathy were excluded from the study
Statistical analysis included calculating crude incidence rates with 95% confidence intervals of overall diabetic retinopathy. Additionally, Cox proportional hazard regression models were used to calculate hazard ratios (HRs) of incident diabetic retinopathy in patients taking GLP-1 agonists compared to patients taking two or more oral glucose-lowering agents, as well as compared to those on insulin therapy.
A total of 10,763 patients newly diagnosed with diabetic retinopathy were included in the results analysis. Compared with patients on two or more oral antidiabetic drugs, those taking GLP-1 agonists did not show a higher risk of diabetic retinopathy (HR 1.00, 95% CI 0.85-1.17). When compared to insulin, patients taking GLP-1 agonists showed a 33% decrease in risk of diabetic retinopathy.
Based on the compelling results from a large cohort of patients with type 2 diabetes and diabetic retinopathy, investigators were able to confidently discern that the use of GLP-1 agonists was not associated with an increased risk of diabetic retinopathy compared to other antidiabetic agents. Investigators did note, however, that much more extensive research should be conducted in order to distinguish length of therapy with incidence rates, as these agents continue to be utilized for long-term therapy.
- Patients taking a GLP-1 agonist did not show an increased risk of diabetic retinopathy compared to those on two or more glucose-lowering agents.
- Compared to insulin use, GLP-1 agonists were associated with a 33% decreased risk of diabetic retinopathy.
- Investigation of glucose-lowering agents in relation to duration of therapy should be conducted to further evaluate the risk for diabetic retinopathy.
Prasad-Reddy, L., Isaacs, D., A (2015). A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs in Context, 4 doi: 10.7573/dic.212283.
Lee, R., Wong, T.Y., Sabanayagam, C. (2015) Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye and Vision, 2 (17). doi: 10.1186/s40662-015-0026-2.
Douros A, Filion KB, Yin H, et al. Glucagon-like peptide-1 receptor agonists and the risk of incident diabetic retinopathy [published online August 27, 2018]. Diabetes Care. 2018. doi: 10.2337/dc17-2280.
Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy