Diabetes Metab J.  2023 May;47(3):394-404. 10.4093/dmj.2022.0221.

Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

• Lin TY
• Kang EYC
• Shao SC
• Lai ECC
• Garg SJ
• Chen KJ
• Kang JH
• Wu WC
• Lai CC
• Hwang YS

• KMID: 2542516
• DOI: http://doi.org/10.4093/dmj.2022.0221

Abstract

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.

Keyword

Diabetic retinopathy; Glucagon-like peptide-1 receptor; Retrospective studies; Sodium-glucose transporter 2 inhibitors

Figure

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  Fig. 1 Selection process of study population. DM, diabetes mellitus; GLP1-RA, glucagon-like peptide-1 receptor agonist; SGLT2i, sodium-glucose cotransporter-2 inhibitor; HbA1c, glycosylated hemoglobin.

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  Fig. 2 Cumulative event rate of (A) proliferative diabetic retinopathy and (B) composite surgical outcome in patients with type 2 diabetes mellitus taking sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonist (GLP1-RA) in the inverse probability of treatment weighting-adjusted cohort. CI, confidence interval.

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  Fig. 3 Long-term change in (A) glycosylated hemoglobin (HbA1c) and (B) estimated glomerular filtration rate (eGFR) among patients with type 2 diabetes mellitus taking sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonist (GLP1-RA) in the inverse probability of treatment weighting-adjusted cohort.

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