Protective Effects of Diabetes Rx Evaluated

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In a population-based study, researchers in the Netherlands found that people who were being treated for their type 2 diabetes were less likely to develop open-angle glaucoma (OAG) and age-related macular degeneration (AMD) than were their untreated counterparts or those without the disease.¹ However, the study results did not show a similar association with the risk of cataract development.

Although this is not the first study to find these protective effects, it drew on more than two decades of follow-up from the Rotterdam Study, allowing a better understanding of exposure time before disease diagnosis. “Our findings accentuate the potential role of diabetes medication in the pathogenesis of OAG and AMD,” said coauthors Eric F. Thee, MD, and Joëlle E. Vergroesen, MSc, at Erasmus University Medical Center in Rotterdam.

SURPRISE FINDING. Otherwise healthy patients were more likely to develop OAG (shown here) and AMD during their lifetimes than were those who were being treated for type 2 diabetes. (Arrow = flame-shaped hemorrhage in the left optic nerve head at the 5-o’clock position.)

Study specifics. The researchers evaluated the records of 11,260 people who participated in the Rotterdam Study from 1990 to 2014. OAG, AMD, and cataract were diagnosed in 4.4%, 17.6%, and 37.3% of the participants, respectively.

Untreated type 2 diabetes was associated with a higher risk of all three diseases: OAG (odds ratio [OR], 1.50), AMD (OR, 1.35), and cataract (OR, 1.63). In contrast, those who received metformin, a first-line treatment for type 2 diabetes, had an 82% lower risk of developing OAG (OR, .18), and those treated with sulfonylureas and insulin (either as monotherapy or in combination) had a 68% lower risk of developing AMD (OR, .32). No protec­tive association was found between diabetes medica­tions and cataract develop­ment.

An unexpected finding. Moreover, those who were being treated for their diabetes had lower lifetime risks of OAG and AMD than did their nondiabetic counterparts. Specifically, the lifetime risk of OAG was lower for individuals taking metformin than for nondiabetics (1.5% vs. 7.2%), while the lifetime risk of AMD was lower for those taking insulin or sulfony­lureas than for nondiabetics (7.05% vs. 33.1%). Dr. Vergroesen described this finding as “most surprising.” He added, “This was unexpected.”

More than metformin. To date, stud­ies exploring this topic have highlighted the protective effect of only metformin in OAG and AMD, Dr. Thee said, while associations with other diabetes med­ications have been overlooked. “These findings suggest that the protective effect [of diabetes medications] found in eye diseases is not per se specific to only one medication.”

Difficult to study. On one hand, the findings spur interest in the protective effect of metformin and other diabe­tes medications, the researchers said. On the other, although randomized clinical trials could confirm causality, the research team is not planning an interventional trial at this time. They cited several hurdles to such a trial, including the safety of treating nondia­betics with diabetes medications as well as the ethical concerns of randomizing diabetes patients to a no treatment cohort.

—Miriam Karmel

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1 Vergroesen JE et al. JAMA Ophthalmol. Pub­lished online May 19, 2022.

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Relevant financial disclosures—Drs. Thee and Vergroesen: None.

For full disclosures and the disclosure key, see below.

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