Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Background Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist used to treat patients with type 2 diabetes mellitus (T2DM). The SUSTAIN 6 trial found a significantly higher rate of retinopathy complications in the semaglutide-treated group compared with the placebo group. Objective This study aimed to evaluate the association between semaglutide and the risk of retinopathy in patients with T2DM. Methods Electronic databases were systematically searched up to April 2021 to identify randomized controlled trials that reported diabetic retinopathy (DR) events in semaglutide-treated and control groups. A meta-analysis was conducted using Review Manager 5.4 software to calculate the risk ratio (RR) and 95% confidence intervals (CIs). Results A total of 23 randomized trials involving 22,096 patients with T2DM were included. There were 730 incident DR cases-463 in the semaglutide group and 267 in the control group. Overall, semaglutide was not associated with increased DR risk compared with controls when all trials were combined (RR 1.14, 95% CI 0.98-1.33). Subgroup analysis showed that semaglutide was associated with an increased risk of DR compared with placebo (RR 1.24, 95% CI 1.03-1.50). Moreover, patient age >= 60 years and diabetes duration >= 10 years were also factors for increased risk of DR when using semaglutide (RR 1.27, 95% CI 1.02-1.59; RR 1.28, 95% CI 1.04-1.58, respectively). Conclusions Semaglutide was not associated with an increased risk of DR; however, caution regarding DR risk is needed for older patients or those with long diabetes duration when taking semaglutide.