Researchers continue to uncover ocular effects—some positive, some negative—from diabetes drugs. This study explored a possible protective effect against glaucoma development in drugs like semaglutide. A bias toward high socioeconomic status patients may have influenced the findings, however. Photo: Novo Nordisk. Click image to enlarge.

The use of semaglutide and other glucagon-like peptide (GLP-1) receptor agonist drugs to treat type 2 diabetes and obesity has rapidly increased in recent years. Type 2 diabetes is a risk factor for glaucoma development, as oxidative stress occurs in both diseases. Previous studies have shown the effects of GLP-1 receptor agonists in reducing IOP and providing some neuroprotection  in glaucoma in preclinical models, both in the brain and retina. However, no previous meta-analysis with this focus was identified. Researchers in Brazil recently performed a systematic meta-analysis that found GLP-1 receptor agonist use was associated with reduced glaucoma development in four out of five retrospective studies. Their findings were recently published in American Journal of Ophthalmology.

Of 194 papers published between July 1991 and May 2024, five retrospective studies met the inclusion criteria, with a total of 156,042 participants based on routinely collected electronic data. Overall, 68,259 (43.7%) were in the GLP-1 receptor agonist group and 87,783 (56.3%) in the control group. With all five studies, the meta-analysis revealed no significant statistical difference in glaucoma incidence among GLP-1 agonists users compared to controls (hazard ratio; HR: 0.78).

However, during a technique called leave-one-out sensitivity analysis, in which each study in turn is excluded to see the effects of such a change, the inclusion of Shao et al. yielded opposite effects, suggesting that SGLT-2 inhibitors might be as effective as, or potentially more effective than, GLP-1 agonists in preventing glaucoma. When this study was excluded from the analysis, the results demonstrated a significant reduction in the incidence of glaucoma among GLP-1 users compared to controls, with reduced heterogeneity (HR 0.71).

The study authors suggested in their paper that, “The change in effect size and heterogeneity is likely due to the inclusion criteria in Shao et al.’s study, which required the control group to use SGLT-2 inhibitors for type 2 diabetes management, unlike the control groups in other included studies.”

The team also highlighted that a key limitation in these studies was the potential for socioeconomic and age-related biases. “GLP-1 receptor agonist drugs are expensive and may be less accessible to lower-income populations, who are at a higher risk of developing glaucoma,” they wrote. “The limited number of studies restricts the study's ability to cover a diverse spectrum of the population and its various characteristics, possibly excluding critical factors necessary for a more precise conclusion on the topic.”

Doctors assessing whether to prescribe GLP-1 receptor agonist use for managing type 2 diabetes should consider the patient's susceptibility to glaucoma, as these often overlap with risk factors for diabetes-related complications like diabetic retinopathy. This integrated approach could help in making more informed treatment decisions.