SGLT2 Inhibitors Shown to Reduce Risk of Glaucoma as well as Treatment Burden

Potential mechanisms proposed by the researchers include aqueous humor reduction through diuretic effects, improved blood flow to the optic nerve head and the reduction of systemic comorbidities that can contribute to glaucoma development, such as cardiovascular and kidney disease. Photo: James L. Fanelli, OD. Click image to enlarge. With research increasingly showing that the popular diabetes drug metformin may have a protective effect against glaucoma, Taiwanese investigators wondered whether another diabetes mainstay, sodium-glucose cotransporter-2 (SGLT2) inhibitors, might also confer a similar benefit. They found that SGLT2 inhibitor use was indeed associated with a protective effect, and in fact it was more pronounced than that of metformin. The findings were reported last week in American Journal of Ophthalmology.Patient data was taken from 160 healthcare organizations across 21 countries of adults with type 2 diabetes who initiated SGLT2 inhibitors or metformin between 2013 and 2023. The researchers performed 1:1 propensity score matching to balance age, sex, race, glycated hemoglobin, body mass index, medications and comorbidities between the groups.The findings showed that diabetes patients receiving SGLT2 inhibitors demonstrated a lower hazard ratio (HR) for ocular hypertension (HR: 0.73), POAG (HR: 0.64) and the need for glaucoma medications (HR: 0.76) compared with those receiving metformin. This was consistent across five years of annual follow-up visits and remained statistically significant in certain cohorts, notably anyone aged 60 and older, white patients and those taking the SGLT2 inhibitor Jardiance (empagliflozin) specifically. “The higher prevalence of glaucoma in older adults may amplify the potential protective effects of SGLT2 inhibitors and lead to more substantial reduction in hazard rates,” the researchers noted in their AJO paper.Several mechanisms could explain the possible protective effect of SGLT2 inhibitors on glaucoma. First, these drugs are characterized by an osmotic diuretic effect that prevents heart failure, protects renal function and lowers blood pressure. “We hypothesize that the diuretic effect of SGLT2 inhibitors might also reduce the amount of aqueous humor, thereby lowering intraocular pressure (IOP),” the researchers wrote. “These effects may be similar to the mechanisms of other osmotic diuretics, such as mannitol, isosorbide and glycerol, in reducing IOP. The hypothesized effect of SGLT2 inhibitors in reducing IOP may alleviate the compression of the optic nerve head, thus lowering the risk of glaucoma.”Second, the cardiovascular benefits of the inhibitors may offer protection against glaucoma through the vascular theory. “Given that impaired ocular blood supply due to arteriosclerosis has been identified as a risk factor for glaucomatous optic neuropathy, it is plausible to assert that reducing vascular obstruction through the use of SGLT2 inhibitors could also lower the risk of glaucoma,” the authors wrote.Third, SGLT2 inhibitors may indirectly lower glaucoma risk by preventing cardiovascular and renal diseases. Studies show they have been shown to effectively reduce the occurrence of major adverse cardiovascular events, renal composite outcomes, systolic blood pressure, diastolic blood pressure and body weights. Because type 2 diabetes, hypertension, chronic kidney disease and obesity are all risk factors for glaucoma, “reducing the onset of these conditions may also lower the risk of glaucoma development,” the authors explained in their paper.The authors observed differing effectiveness among different meds within the SGLT2 inhibitor class. Empagliflozin and dapagliflozin are associated with a significantly reduced risk of POAG, while canagliflozin is not. “Studies have indicated that empagliflozin and dapagliflozin have higher SGLT2 selectivity than canagliflozin, which may contribute to its potential role in glaucoma prevention,” the researchers noted.Additionally, they added that the study consisted of smaller sample sizes of patients prescribed canagliflozin compared to those prescribed empagliflozin and dapagliflozin, which may explain the lack of a significant association between dapagliflozin and canagliflozin in the development of POAG.Click here for the journal source. Pan S-Y, Weng C-H, Tsai S-F, et al. Comparative risk of glaucoma in patients using sodium-glucose cotransporter-2 inhibitors and metformin: a multinational cohort study. Amer J Ophthalmol. September 19, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.