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Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists
Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang
Diabetes Metab J. 2023;47(3):394-404.   Published online March 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0221
  • 8,322 View
  • 337 Download
  • 17 Web of Science
  • 19 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.
Methods
This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR.
Results
There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70).
Conclusion
Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

Citations

Citations to this article as recorded by  
  • Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications
    Ehsan Rahimy, Euna B. Koo, Karen M. Wai, Cassie A. Ludwig, Andrea L. Kossler, Prithvi Mruthyunjaya
    American Journal of Ophthalmology.2025; 270: 93.     CrossRef
  • Incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta‐analysis of observational studies
    Samuel Igweokpala, Naheemot Olaoluwa Sule, Antonios Douros, Oriana H. Y. Yu, Kristian B. Filion
    Diabetes, Obesity and Metabolism.2024; 26(2): 721.     CrossRef
  • Association of sodium–glucose cotransporter‐2 inhibitors and the risk of retinal vascular occlusion: A real‐world retrospective cohort study in Taiwan
    Tzu‐Yi Lin, Eugene Yu‐Chuan Kang, Shih‐Chieh Shao, Edward Chia‐Cheng Lai, Nan‐Kai Wang, Sunir J. Garg, Kuan‐Jen Chen, Je‐Ho Kang, Wei‐Chi Wu, Chi‐Chun Lai, Yih‐Shiou Hwang
    Diabetes/Metabolism Research and Reviews.2024;[Epub]     CrossRef
  • Risk of rotator cuff tear and rotator cuff repair surgery comparison between sodium-glucose cotransporter 2 inhibitors and glucagon like peptide-1 receptor agonists: A real-world study
    Yu-Chi Su, Pei-Chun Hsieh, Edward Chia-Cheng Lai, Yu-Ching Lin
    Diabetes & Metabolism.2024; 50(2): 101522.     CrossRef
  • Optimising renal risk parameters in type 2 diabetes mellitus: Perspectives from a retinal viewpoint
    Sarita Jacob, George I. Varughese
    Clinical Medicine.2024; 24(2): 100031.     CrossRef
  • Risk of diabetic retinopathy and diabetic macular oedema with sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database
    Aikaterini Eleftheriadou, David Riley, Sizheng S. Zhao, Philip Austin, Gema Hernández, Gregory Y. H. Lip, Timothy L. Jackson, John P. H. Wilding, Uazman Alam
    Diabetologia.2024; 67(7): 1271.     CrossRef
  • Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study
    Karen M. Wai, Kapil Mishra, Euna Koo, Cassie Ann Ludwig, Ravi Parikh, Prithvi Mruthyunjaya, Ehsan Rahimy
    American Journal of Ophthalmology.2024; 265: 39.     CrossRef
  • Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy
    Andrew J. Barkmeier, Jeph Herrin, Kavya Sindhu Swarna, Yihong Deng, Eric C. Polley, Guillermo E. Umpierrez, Rodolfo J. Galindo, Joseph S. Ross, Mindy M. Mickelson, Rozalina G. McCoy
    Ophthalmology Retina.2024; 8(10): 943.     CrossRef
  • Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study
    Tzu-Yi Lin, Eugene Yu-Chuan Kang, Nan-Kai Wang, Je-Ho Kang, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang
    Biomedical Journal.2024; : 100771.     CrossRef
  • Association between sodium-glucose cotransporter 2 inhibitors and eye disorders: a systematic review and meta-analysis
    Bo Xu, Bo Kang, Fan Tang, Jiecan Zhou, Zunbo He
    Expert Review of Clinical Pharmacology.2024; 17(10): 949.     CrossRef
  • Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome
    Ishani Kapoor, Swara M. Sarvepalli, David A. D'Alessio, Majda Hadziahmetovic
    Clinical & Experimental Ophthalmology.2024;[Epub]     CrossRef
  • Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data
    Masaya Koshizaka, Tomoaki Tatsumi, Fumiko Kiyonaga, Yoshinori Kosakai, Yoko Yoshinaga, Mami Shintani-Tachi
    Diabetes Therapy.2024; 15(11): 2401.     CrossRef
  • NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY
    Rithwick Rajagopal, Janet B. McGill
    Retina.2024; 44(11): 1851.     CrossRef
  • SGLT2 inhibitors and diabetic retinopathy: Insights from the management of nephropathy
    Maria S. Varughese, Lakshminarayanan Varadhan
    Eye.2024;[Epub]     CrossRef
  • Mechanism and therapeutic targets of circulating immune cells in diabetic retinopathy
    Bowen Zhao, Yin Zhao, Xufang Sun
    Pharmacological Research.2024; 210: 107505.     CrossRef
  • Diabetes Renders Photoreceptors Susceptible to Retinal Ischemia-Reperfusion Injury
    David A. Antonetti, Cheng-Mao Lin, Sumathi Shanmugam, Heather Hager, Manjing Cao, Xuwen Liu, Alyssa Dreffs, Adam Habash, Steven F. Abcouwer
    Investigative Ophthalmology & Visual Science.2024; 65(13): 46.     CrossRef
  • Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
    Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Yih-Shiou Hwang
    Diabetes & Metabolism Journal.2023; 47(4): 573.     CrossRef
  • Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
    Jihee Ko, Sun Joon Moon
    Diabetes & Metabolism Journal.2023; 47(4): 571.     CrossRef
  • Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes
    Fu-Shun Yen, James Cheng-Chung Wei, Teng-Shun Yu, Yu-Tung Hung, Chih-Cheng Hsu, Chii-Min Hwu
    JAMA Network Open.2023; 6(12): e2348431.     CrossRef
Drug/Regimen
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Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus
Ja Young Jeon, Kyoung Hwa Ha, Dae Jung Kim
Diabetes Metab J. 2021;45(4):505-514.   Published online October 30, 2020
DOI: https://doi.org/10.4093/dmj.2020.0057
  • 9,091 View
  • 378 Download
  • 11 Web of Science
  • 12 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.
Methods
This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs).
Results
After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.
Conclusion
SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by  
  • Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and cerebrovascular diseases: a meta-analysis of controlled clinical trials
    Fei Wang, Chunyu Li, Lili Cui, Shuo Gu, Junyu Zhao, Haipeng Wang
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Evaluation and Management of Patients With Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
    Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
    International Journal of Heart Failure.2023; 5(1): 1.     CrossRef
  • Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
    Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 10.     CrossRef
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    International Journal of Molecular Sciences.2023; 24(17): 13381.     CrossRef
  • Cardioprotective effects of dipeptidyl peptidase-4 inhibitors versus sulfonylureas in addition to metformin: A nationwide cohort study of patients with type 2 diabetes
    Jui Wang, Hon-Yen Wu, Kuo-Liong Chien
    Diabetes & Metabolism.2022; 48(3): 101299.     CrossRef
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    Journal of Diabetes Investigation.2022; 13(4): 614.     CrossRef
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    Chang Hee Kwon, Ye-Jee Kim, Min-Ju Kim, Myung-Jin Cha, Min Soo Cho, Gi-Byoung Nam, Kee-Joon Choi, Jun Kim
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