SGLT2 Inhibitor Use May Lower Risk for Dry Eye Disease in People with T2D

Jia-Horung Hung, MD

Treatment of type 2 diabetes (T2D) with sodium-glucose cotransporter 2 (SGLT2) inhibitors may lead to lower risk for dry eye disease (DED), compared with glucagon-like peptide-1 receptor agonists (GLP-1 RA).

The new data from a large clinical cohort study suggest a 22% lower risk of DED with SGLT2 inhibitor use, rather than GLP-1 RA use.

“Given that DED affects about one-fifth of patients with T2D and reduces the patients’ quality of life, our findings with the small absolute risk difference (2.5 per 1000 person-years) between SGLT2 inhibitors and GLP-1 RAs may provide an important reference for clinical decisions about prescribing different antidiabetic medications to delay or prevent DED in patients with T2D,” wrote study author Jia-Horung Hung, MD, Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University.

Some newer drugs have been approved for treatment of DED by the US Food and Drug Administration in 2016 and 2021, yet the influence of antidiabetic drugs on the incidence of DED remains unknown.

As chronic inflammation is a large part of the pathophysiologic process of DED, anti-inflammatory benefits from SGLT2 inhibitors may lower its incidence. The retrospective cohort analysis of an electronic medical record database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or GLP-1 RAs from 2016 to 2018.

Investigators noted that GLP-1 RAs were chosen as the active comparator as they share similar pleiotropic effects with SGLT2 inhibitors. They defined the first data of use of either agent as the index date and the year before the index date as the baseline period.

The primary outcome was identified as the incidence of DED, with follow-up from index until occurrence of DED, last clinical visit, death, or end of the database in December 2021. The analysis included propensity scores based on logistic regression that included that baseline covariate, including age, sex, comorbidities, glucemic controls, and kidney function.

Hung and colleagues included a total of 10,038 patients with T2D newly receiving SGLT2 inhibitors and 1077 patients newly receiving GLP-1 RAs in the analysis. The SGLT2 group included 5689 men (56.7%) with a mean age of 59.5 years, while the GLP-1 RA group included 587 men (54.5%) with a mean age of 58.5 years.

After a mean follow-up of 3.9 years with 391 DED outcomes, investigators observed a difference in the DED incidence between the SGLT2 inhibitor (9.0 events per 1000 patient-years) and the GLP-1 RA (11.5 events per 1000 patient-years). This yielded a hazard ratio of 0.78 (95% confidence interval [CI], 0.68 - 0.89).

They added that they did not find any significant differences between the SGLT2 inhibitor and GLP-1 RA regarding hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR).

Moreover, subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitor use were similar across different age, sex, blood glucose level, and kidney function groups as the main analysis.

The study, “Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients with Type 2 Diabetes in Taiwan,” was published in JAMA Network Open.