1. Patients with Type 2 Diabetes taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have a lower incidence of diabetic retinopathy (DR), compared to those not taking GLP-1 RAs.

2. A Mendelian randomization analysis found that an increase in GLP1R gene expression was associated with decreased risk for background and severe nonproliferative DR subtypes, but not proliferative DR and overall DR.

Evidence Rating Level: 2 (Good)

Diabetic retinopathy (DR) affects greater than 100 million individuals internationally. It can be classified into 3 types (in order of severity): Background DR, severe nonproliferative DR, and proliferative DR. Currently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are diabetes medications associated with reductions in cardiovascular morbidity and mortality, as well as stroke. However, they have also been hypothesized to reduce the risk of DR, since the expression of GLP1R, the target of GLP-1 RAs, are prevalent in the retina. The current population matched cohort study based in Sweden examined the incidence of DR amongst patients with diabetes who did and did not use GLP-1 RAs, and also conducted a summary-data-based Mendelian randomization analysis. The cohort consisted of patients diagnosed with Type 2 Diabetes between 2006 and 2015, with each patient using GLP-1 RAs matched to randomly selected patients not using GLP-1 RAs, matched by age, sex, and duration of disease. The Mendelian analysis used single nucleotide polymorphisms (SNPs) associated with GLP1R expression in the pancreas, and correlated that with DR outcomes. In total, there were 14,119 patients included, with 2390 taking GLP-1 RAs and 11,729 patients who did not use GLP-1 RAs. The median (IQR) follow-up time was 2.03 (1.07-3.18) years for those using GLP-1 RAs and 1.92 (0.99-3.47) years for those not using GLP-1 RAs. The study found that the incidence of DR was 5.97 per 1000 person-years for GLP-1 RA users and 12.85 per 1000 person-years for non-users. Therefore, the incidence of DR was significantly lower in GLP-1 RA users (HR 0.43, 95% CI 0.29-0.61, p < 0.0001). Additionally, the Mendelian randomization analysis found that an increase in GLP1R expression by 1 standard deviation was associated with lower background DR risk (OR 0.83, 95% CI 0.71-0.97, p = 0.0162) and severe nonproliferative DR (OR 0.72, 95% CI 0.53-0.98, p = 0.0355), but not overall DR and proliferative DR. Overall, this study demonstrated through a population-based cohort analysis and a Mendelian randomization analysis that GLP-1 RAs are associated with decreased risk of developing DR.

Click to read the study in BMC Medicine

Image: PD

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