(SLC-004) A Comparative Study of Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors on Renal Disorders in Type 2 Diabetes Mellitus

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are medications that can improve renal and cardiovascular outcomes for people with chronic kidney disease (CKD). However, their preventive effect on renal disease remains uncertain.

Objectives: We aimed to compare the effects of SGLT-2i and Dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risks of chronic kidney disease and nephrolithiasis using the target trial emulation method.

Methods: Using data from the electronic health records in Clinical Practice Research Datalink Aurum, we performed a large-scale, population-based cohort study to compare the risks of chronic kidney disease (stage 3 to 5) and nephrolithiasis between SGLT-2i and DPP-4i among people with type 2 diabetes (T2DM). The propensity-score fine-stratification weighting method was applied along with competing-risk Cox proportional-hazard regression models to obtain crude and adjusted hazard ratios (aHRs) and their corresponding 95% confidence intervals.

Results: Among 1.6 million eligible T2DM participants aged 40 and above, 157,101 SGLT-2i new users were compared with 207,421 DPP-4i new users. SGLT-2i users had lower incidence rates of nephrolithiasis (1.9 per 1000 person - years) and chronic kidney disease (26.5 per 1000 person - years) compared with DPP-4i users (3.4 and 35.6 per 1000 person-years, respectively). The adjusted hazard ratios (HRs) were 0.55 (95% CIs 0.50 to 0.60) for nephrolithiasis and 0.81 (95% CIs 0.79 to 0.83) for chronic kidney disease.

Conclusions: Our study indicates that SGLT-2i, compared to DPP-4is, were associated with a significantly lower risk of both nephrolithiasis and chronic kidney disease in individuals with T2DM. These findings suggest that SGLT-2it could be a valuable option for preventing these renal conditions in individuals with T2DM. However, further research is needed to understand the long-term implications and underlying mechanisms of these associations.