Could a commonly used glucose-lowering therapy influence the short-term risk of a rare optic nerve event in adults with type 2 diabetes mellitus (T2DM)? A pragmatic target trial emulation published in Diabetes Care found that initiation of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) was associated with a higher 1-year risk of nonarteritic anterior ischemic optic neuropathy (NAION) compared with dipeptidyl peptidase 4 (DPP-4) inhibitors.

The active-comparator, new-user cohort used the U.K. Clinical Practice Research Datalink and included 523,227 adults with physician-diagnosed T2DM who newly started either a GLP-1 RA or a DPP-4 inhibitor. DPP-4 inhibitors were selected as the comparator because both drug classes are used as second-line therapy, and DPP-4 inhibitors have no established association with NAION. Analyses used propensity-score fine-stratification weighting to adjust for measured baseline differences.

At 1 year, NAION occurred in 14 of 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 of 416,369 DPP-4 inhibitor initiators (7.2 per 100,000). GLP-1 RA initiation was associated with increased NAION risk (risk ratio [RR], 2.56; 95% CI, 1.44-4.86), with an absolute risk difference (RD) of 11.3 per 100,000. Risk appeared greatest during the first 6 months and declined with longer use. Higher relative risk was observed in younger adults, men, ever-smokers, and those with marked HbA1c reduction.

The analysis found that GLP-1 RA initiation was associated with increased 1-year NAION risk versus DPP-4 inhibitor initiation among adults with T2DM.