Semaglutide, central retinal thickness and continuous glucose monitoring in persons with type 2 diabetes: A post-hoc analysis from a randomised trial.

AIMS: Glycemic control is important for preventing diabetic retinopathy (DR), but rapid improvements could deteriorate the disease. In some, but not all studies, semaglutide is speculated to worsen DR, but the mechanism is unknown. Central retinal thickness (CRT) is an early marker of DR. Therefore, the objective was to investigate whether increased Time in Range (TIR (3.9-10.0 mmol/L)), was associated with reduced CRT in persons treated with semaglutide. METHODS: Forty participants with type 2 diabetes were included in this post-hoc analysis of a 32-week randomised, placebo-controlled, partly open-label trial investigating the separate and combined effects of semaglutide and empagliflozin on target organ damage in 120 participants with type 2 diabetes. Individuals were randomised into four groups: i) semaglutide, ii) empagliflozin, iii) the combination or iv) placebo, n = 30 for each group). In the present study, 10 participants from each of the 4 arms participated. TIR was assessed using Continuous Glucose Measurement for 7-8 days and CRT was assessed using ocular coherence tomography. RESULTS: In the 10 individuals treated with semaglutide, CRT increased ~1 % (3.76 μm, 95%CI [-0.32; 7.85], p = 0.065) compared to placebo. This was attenuated with adjustment for TIR (p = 0.21). Independently of the four interventions, increased TIR remained associated with increased CRT (0.07 μm, 95%CI[0.03; 0.12]μm, p = 0.002). CONCLUSION: Semaglutide treatment did not impact CRT beyond what could be explained by changes in glycaemia. Across all interventions, increased TIR was associated with increases in CRT, thus supporting the link between rapid improved glycemia and DR.