Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes

Author:

Yen Fu-Shun1,Wei James Cheng-Chung234,Yu Teng-Shun56,Hung Yu-Tung56,Hsu Chih-Cheng78910,Hwu Chii-Min1112

Affiliation:

1. Private practice, Taoyuan, Taiwan

2. Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan

3. Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan

4. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

5. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

6. College of Medicine, China Medical University, Taichung, Taiwan

7. Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan

8. Department of Health Services Administration, China Medical University, Taichung, Taiwan

9. Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan

10. National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin County, Taiwan

11. Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

12. Faculty of Medicine, National Yang-Ming Chiao Tung University School of Medicine, Taipei, Taiwan

Abstract

ImportanceDiabetic nephropathy and diabetic retinopathy share many similarities in pathophysiological processes. Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have a protective role in the risk of diabetic retinopathy.ObjectiveTo compare the risk of sight-threatening retinopathy associated with SGLT2is and other second-line glucose-lowering medications (including pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors [DPP-4is]) in patients with type 2 diabetes (T2D).Design, Setting, and ParticipantsThis cohort study in Taiwan applied a new-user and active-comparator design. Patient demographic and clinical data were obtained from the National Health Insurance Research Database. Adult patients with newly diagnosed T2D from January 1, 2009, to December 31, 2019, were recruited and followed up until December 31, 2020. Propensity score matching was used to identify pairs of patients treated with SGLT2i vs DPP-4i, SGLT2i vs pioglitazone, and SGLT2i vs sulfonylurea from January 1, 2016, to December 31, 2019. Data were analyzed between August 18, 2022, and May 5, 2023.ExposuresTreatment with SGLT2i, DPP-4i, pioglitazone, and sulfonylureas starting on January 1, 2016.Main Outcomes and MeasuresThe main outcome was sight-threatening retinopathy in participants. Cox proportional hazards regression models were used to assess relative hazards of sight-threatening retinopathy between the matched case and control groups.ResultsA total of 3 544 383 patients with newly diagnosed T2D were identified. After 1:1 propensity score matching, 65 930 pairs of patients treated with SGLT2i vs DPP-4i, 93 760 pairs treated with SGLT2i vs pioglitazone, and 42 121 pairs treated with SGLT2i vs sulfonylurea were identified. These matched patients included 236 574 males (58.6%), with a mean (SD) age of 56.9 (11.8) years. In the matched cohorts, SGLT2i had a significantly lower risk of sight-threatening retinopathy than DPP-4i (adjusted hazard ratio [AHR], 0.57; 95% CI, 0.51-0.63), pioglitazone (AHR, 0.75; 95% CI, 0.69-0.81), and sulfonylureas (AHR, 0.62; 95% CI, 0.53-0.71). The Kaplan-Meier curves showed that SGLT2i was associated with a significantly lower cumulative incidence of sight-threatening retinopathy than DPP-4i (3.52 vs 6.13; P < .001), pioglitazone (4.32 vs 5.76; P < .001), and sulfonylureas (2.94 vs 4.67; P < .001).Conclusions and RelevanceThis cohort study found that SGLT2i was associated with a lower risk of sight-threatening retinopathy compared with DPP-4i, pioglitazone, and sulfonylureas. This finding suggests that SGLT2i may play a role not only in reduced risk of diabetic nephropathy but also in the slow progression of diabetic retinopathy in patients with T2D.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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