Incidence of dry eye reduced with SGLT2 inhibitors

A potential benefit of SGLT2 inhibitors in patients with type 2 diabetes (T2D) may be a reduced incidence of dry eye, the authors of a large retrospective study said.

In over 10,000 patients followed for approximately 4 years, the incidence of dry eye was lower in those receiving SGLT2 inhibitors compared to GLP-1 receptor agonists (9.0 versus 11.5 events per 1 000 person-years), said Jia-Horung Hung, MD, of National Cheng Kung University Hospital in Taiwan, and colleagues.

As they reported in the study of Open JAMA Networkthe 22% risk reduction (HR 0.78, 95% CI 0.68-0.89) was generally maintained in all subgroups, although there were greater risk reductions in men (HR 0.62, 95% CI 0.51-0.75) and in patients with better renal function (HR 0.62, 95% CI 0.51-0.77).

“Since DED [dry eye disease] affects about one-fifth of patients with T2D and reduces patients’ quality of life, our results with the small absolute risk difference (2.5 per 1,000 person-years) between SGLT2 inhibitors and GLP-1 ARs [receptor agonists] may provide an important reference for clinical decisions regarding the prescription of different antidiabetic drugs to delay or prevent DED in patients with T2DM,” the researchers wrote.

“Furthermore, similar changes in glycemic control and renal function for SGLT2 inhibitors and GLP-1 ARs imply that possible mechanisms underlying the lower incidence of DED due to the use of SGLT2 inhibitors SGLT2 are independent of these factors,” the researchers said.

They explained that chronic inflammation plays a major role in dry eye and that SGLT2 inhibitors may have anti-inflammatory effects on the ocular surface.

Additionally, DED has been associated with pro-inflammatory M1 polarized macrophages and elevated levels of inflammatory cytokines. But SGLT2 inhibitors have been reported to reduce the accumulation of polarized M1 macrophages while inducing the anti-inflammatory phenotype of M2 macrophages. SGLT2 inhibitors have also been shown to lower inflammatory cytokine levels by inducing low-grade serum ketones, the researchers noted.

“This action could explain the greater reduction in DED risk with SGLT2 inhibitors compared to GLP-1 ARs,” Hung’s group said. Previous studies have reported that SGLT2 inhibitors reduce the risk of other inflammatory eye diseases, such as diabetic retinopathy, diabetic macular edema, and glaucoma.

Therefore, “clinicians can also assess the risks of ophthalmologic conditions when selecting antidiabetic drugs as intensification therapy to optimize treatment benefit,” Hung and co-authors suggested.

They retrospectively analyzed information from the largest multi-institutional database in Taiwan, which contained information on 10,038 patients with T2D who received SGLT2 inhibitors and 5,608 who received GLP-receptor agonists. 1. Almost half were women and the average age was around 59. Clinical factors, such as blood sugar control and kidney function, were similar in the two groups.

The primary outcome measure was the incidence of dry eye as determined by International Classification of Diseases codes and prescriptions of drugs used to treat the disease. The researchers used Cox proportional hazards regression models to examine associations between the primary outcome and the type of diabetes medication as well as various clinical factors.

Discussing the greater reductions in dry eye risk seen in men and in patients with better kidney function, the researchers noted that the incidence of dry eye was 1.5 times higher in women than in men. men and twice as high in patients with reduced renal function (estimated glomerular filtration rate less than 90 ml/min/1.73 m2) compared to those that perform better. This could have masked the reduced risk in these groups and accentuated it in their counterparts, the investigators explained.

They noted that women might be more susceptible to developing dry eye due to systemic factors, such as lower androgen levels and a higher prevalence of autoimmune diseases. Similarly, patients with renal insufficiency or proteinuria may be at increased risk of developing this condition due to tear hyperosmolarity and increased ocular surface inflammation.

“Because there were no significant differences in the risks of DED between the use of SGLT2 inhibitors and GLP-1 receptor agonists in women with T2DM or patients whose renal function was degraded, the prescription of SGLT2 inhibitors for these populations at high risk of DED should be based on other clinical considerations,” Hung and co-authors advised.

A notable limitation of the study, they said, was the much larger size of the SGLT2 inhibitor group, which may have masked greater heterogeneity in this group compared to the GLP-1 group.

“Furthermore, due to the nature of the retrospective study design, we did not assess clinical types in patients developing DED,” the team wrote. “Further studies with predefined clinical and instrumental diagnostic evaluation are suggested to investigate the role of SGLT2 inhibitors in the incidence of DED.”

  • Jeff Minerd is a freelance medical and science writer based in Rochester, NY.


The study was supported by the National Cheng Kung University Hospital and the Ministry of Science and Technology.

Hung and his co-authors reported no conflict of interest disclosures.

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