Background/Aims: Type 2 diabetes mellitus (T2DM) is an extremely prevalent disease with multisystem complications. We aim to compare the effects of two common glucose lowering medications; sodium glucose co-transporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I), on the incidence of diabetic retinopathy and cataracts in T2DM patients in Hong Kong. Methods: Retrospective population-based cohort study of T2DM patients treated with SGLT2I or DPP4I between 1st January 2015 and 31st December 2020. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed on demographics, past co-morbidities, number of prior hospitalizations, duration from T2DM diagnosis to intial drug exposure, non-SGLT2I/DPP4I medications (including other anti-diabetes drugs), abbreviated modification of diet in renal disease, HbA1c, fasting glucose, and their time-weighted means. Sensitivity analysis using a one-year lag time and competing risk analyses using cause-specific and sub-distribution hazard models were conducted. Results: This study cohort included 26 165 SGLT2I and 42 796 DPP4I users (total: N=68 961 patients; 56.43% males, median age: 62.0 years old (standard deviation (SD): 12.8)). Over a median follow-up of 5.56 years (IQR: 5.24-5.80) and after propensity score matching (SGLT2I: N=26 165; DPP4I: N=26 165), SGLT2I users had lower incidences of cataract (4.54% vs. 6.64%%, standardised mean difference [SMD]=0.09) and diabetic retinopathy (3.65 vs. 6.19, SMD=0.12) compared to DPP4I users. SGLT2I use was associated with lower risks of new onset cataract (HR: 0.67, 95% CI: [0.62-0.72] P<0.0001) and diabetic retinopathy (hazard ratio [HR]: 0.57, 95% confidence interval [CI]: [0.53-0.62], P<0.0001). These associations remained significant on multivariable Cox regression ;cataract: HR: 0.69, 95% CI: 0.64-0.75 (P<0.0001); diabetic retinopathy: HR: 0.68, 95% CI: 0.63-0.75 (P<0.0001). Conclusions: Amongst T2DM patients in Hong Kong, SGLT2I use was associated with lower risks of new onset cataract or diabetic retinopathy compared to DPP4I use.

The authors have declared no competing interest.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKWC IRB) (UW-20-250) and complied with the Declaration of Helsinki.

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The data that support the findings of this study were provided by the Hong Kong Hospital Authority, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Hong Kong Hospital Authority.