GLP-1RAs up risk for ischaemic optic neuropathy in T2D patients

The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) results in an increased risk for ischaemic optic neuropathy (ION) at 18 months when compared with the use of sodium‒glucose cotransporter-2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is), reports a study.

However, the absolute risk remains very low, and the observed differences may indicate residual confounding, according to the investigators.

This observational emulation of a target trial was conducted using a large US-based commercial claims database from January 2017 to December 2022. Adult patients (aged 18‒65 years) with type 2 diabetes (T2D) initiating a GLP-1RA, an SGLT2i, or a DPP4i were identified.

Incident ION served as a proxy for nonarteritic anterior ION and the primary outcome. The investigators adjusted analyses for more than 80 covariates using inverse probability of treatment weights and estimated the 18-month cumulative incidence and risk differences (RDs) per 10,000 patients.

At 18 months, the ION risk was higher among users of GLP-1RA than of SGLT2i (8.5 vs 5.5 per 10,000 patients; RD, 3.0, 95 percent confidence interval [CI], 0.4‒5.7) and DPP4i (7.8 vs 4.2 per 10,000 patients; RD, 3.6, 95 percent CI, 1.1‒6.1). The numbers needed to harm were 3,333 and 2,778, respectively.

Of the 81 ION events among GLP-1RA users, 69 (85.2 percent) occurred in persons >50 years of age and 57 (70.3 percent) in men.

Furthermore, RDs decreased among users of metformin monotherapy (2.0 and 4.1) vs two or more diabetes medications (5.7 and 4.0) when compared with SGLT2is and DPP4is, respectively. RDs were also higher in men, older patients, and those with cardiovascular disease or ophthalmic conditions, with minimal differences in women and those <50 years of age.

The study was limited by the absence of diagnostic codes specifically for nonarteritic anterior ION. “Missing data on key clinical factors (such as BMI and T2D duration) may contribute to residual confounding, leaving uncertainty about whether the observed association is causal,” the investigators said.