Lower Risk of Incident Cataracts and Diabetic Retinopathy amongst Individuals Treated with Sodium Glucose Cotransporter-2 Inhibitor Compared to Dipeptidyl Peptidase-4 Inhibitor in Type 2 Diabetes Mellitus

Background/AimsType 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. MethodsRetrospective 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. ResultsThis 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). ConclusionsAmongst T2DM patients in Hong Kong, SGLT2I use was associated with lower risks of new onset cataract or diabetic retinopathy compared to DPP4I use. Synopsis/PrecisSodium glucose cotransporter-2 inhibitor (SGLT2I) use was associated with lower rates of new onset diabetic retinopathy and cataracts compared to dipeptidyl peptidase-4 inhibitor (DPP4I) use in patients with type 2 diabetes melllitus (T2DM) from Hong Kong. What is already known on this topicVarious glucose lowering medications may have additional beneficial or aggravating properties for/against diabetic retinopathy and cataract formation in diabetic populations beyond their glucose lowering capabilities. What this study addsThis study showed that SGLT2I use was associated with significantly lower rates of new onset cataracts and diabetic retinopathy when compared to DPP4I use in a T2DM population in Hong Kong. Additionally, to the best of our knowledge, this is the first population-based study on the effects of SGLT2I and DPP4I use on the development of cataracts in individuals with T2DM. How this study might affect research, practice or policyThis study provides preliminary data for further evaluation of SGLT2I and DPP4I use in preventing the incidence and progression of cataracts and diabetic retinopathy in a T2DM individuals. This study may also aid clinicians in deciding between SGLT2 and DPP4I if microvascular retinal complications and cataracts are a concern in individual cases.