Abstract
Purpose
To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care.
Methods
A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure.
Results
A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor–exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR].
Conclusion
Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.
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Funding
University of Pennsylvania Core Grant for Vision Research (2P30EY001583). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional funding was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. Funding from each of the above sources was received in the form of block research grants to the Scheie Eye Institute. None of the organizations had any role in the design or conduction of the study.
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All handling of the data used in this study involving human participants was in accordance with the ethical standards of the University of Pennsylvania and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was deemed exempt from review by the Institutional Review Board at the University of Pennsylvania due to the de-identified nature of the data.
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The need for informed consent was waived due to the de-identified nature of the data.
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Brian VanderBeek previously consulted for EyePoint Pharmaceuticals. Charles Miller is an employee of Regeneron Pharmaceuticals. No other financial relationships or potential conflicts exist for any author.
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Portions of this research were presented at the ARVO Annual Meeting in 2022. The abstract was published in Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2169 – F0232.
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Nadelmann, J.B., Miller, C.G., McGeehan, B. et al. SGLT2 inhibitors and diabetic retinopathy progression. Graefes Arch Clin Exp Ophthalmol 262, 753–758 (2024). https://doi.org/10.1007/s00417-023-06273-0
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DOI: https://doi.org/10.1007/s00417-023-06273-0