SGLT2 Inhibitors May Reduce Diabetic Retinopathy Risk, Study Finds

Credit: Marc Schulte/Pexels

The risk of diabetic retinopathy appeared lower in patients with type 2 diabetes (T2D) treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors than those receiving dipeptidyl peptidase 4 (DPP4) inhibitors, according to new research.¹

Across the nationwide cohort in Taiwan, the analysis showed the SGLT2 inhibitor cohort experienced a substantially lower risk of diabetic retinopathy, compared to those who used DPP4 inhibitors, across both the early and late stages of the disease.

“SGLT2 inhibitors appeared to decelerate the progression of diabetic retinopathy, irrespective of whether it was in its early or late stage,” wrote the investigative team, led by Tung-Min Yu, MD, PhD, division of nephrology, Taichung Veterans General Hospital.

Available treatments for ophthalmic diseases are generally focused on late-stage disease states. There are little to no effective treatments to reduce progression once diabetic retinopathy occurs, making preventive therapies critical for reducing vision loss. Adequate metabolic control is considered the treatment choice for the prevention of diabetic retinopathy, including intensive blood glucose and hyperlipidemia control.²

SGLT2 inhibitors are used in practice for cardiorenal protection but are considered to have additional benefits on various complications, including macular edema. For those with diabetes, both SGLT2 inhibitors and DPP-4 inhibitors are considered second-line, add-on oral hypoglycemia medications. However, there is little evidence on the effect of SGLT2 inhibitors on the progression of diabetic retinopathy, including early development and late progression.³

For this nationwide retrospective cohort study, investigators extracted secondary data from the Taiwan National Health Insurance Research Database (May 2016 – December 2018), identifying a total of 1,101,002 patients.¹ After applying exclusion criteria, the study population comprised 31,772 SGLT2 inhibitor users and 202,052 DPP4 inhibitor users. Among those treated with SGLT2 inhibitors, 61.6% were men, with a mean age of 53.7 years and a mean duration of T2D of 6.7 years.

To achieve balance and account for heterogeneity, the team performed propensity score matching in a 1:1 ratio, adjusting for factors including age, sex, comorbidities, and anti-diabetic medication use. Propensity score matching left a total of 31,764 patients receiving SGLT2 inhibitors and 31,764 patients receiving DPP4 inhibitors in the study.

Upon analysis, investigators observed 919 diabetic retinopathy events among the propensity score-matched cohorts during follow-up. The overall incidence rate of diabetic retinopathy was 10.9 per 10,000 patient-years for SGLT2 inhibitor users and 15.6 per 10,000 patient-years for DPP4 inhibitor users.

Among the total cohort, SGLT2 inhibitor users showed a significantly reduced risk of diabetic retinopathy (aHR, 0.68; 95% CI, 0.60 - 0.78), compared with DPP4 inhibitor users. Moreover, the SGLT2 inhibitor user cohort exhibited positive outcomes for both early-stage (aHR, 0.69; 95% CI, 0.60 - 0.81) and late-stage (aHR, 0.64; 95% CI, 0.55 - 0.73) diabetic retinopathy, compared with DPP4 inhibitor users (all P <.001).

Trends from the sensitivity and subgroup analyses were consistent with the primary analysis – data showed a significantly lower risk of diabetic retinopathy, regardless of sex, age <80 years, monthly income, hypertension, hyperlipidemia, and medicine use, among the SGLT2 inhibitor cohort, compared to DPP4 inhibitor users.

Yu and colleagues noted the translation of these findings, while providing valuable insights on the effect of these agents on diabetic retinopathy, is limited, given the lack of information on clinical factors, including glucose control, and the study’s inability to establish a causal relationship due to its observational design.

“Given the unavailability of HbA1c level measurements as a proxy for glycemic control in the claims database employed for this research, future randomized controlled trials are essential to corroborate these findings,” investigators wrote.

References

1. Huang ST, Bair PJ, Chang SS, et al. Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes after SGLT-2 Inhibitors: A Nationwide Population Cohort Study [published online ahead of print, 2023 Oct 7]. Clin Pharmacol Ther. 2023;10.1002/cpt.3074. doi:10.1002/cpt.3074
2. Teo ZL, Tham YC, Yu M, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology. 2021;128(11):1580-1591. doi:10.1016/j.ophtha.2021.04.027
3. American Diabetes Association Professional Practice Committee. 16. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S244-S253. doi:10.2337/dc22-S016