(CSPOT10) Effectiveness and Safety of SGLT2 Inhibitor Treatment on Renal Outcomes in Patients with Type 2 Diabetes: A Nationwide Observational Cohort Study in South Korea

Background: Recent clinical guidelines on type 2 diabetes mellitus (T2DM) have shifted toward a more individualized approach, with a particular emphasis on the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors. These drugs have not only shown promising cardiovascular benefits but also renal outcomes. However, despite their established efficacy, only a few studies have thoroughly investigated their renal effects and safety outcomes.

Objectives: Thus, the present study aimed to address this deficiency by evaluating the effectiveness of SGLT2 inhibitor treatment on renal outcomes compared with dipeptidyl peptidase 4 (DPP4) inhibitor treatment using large-scale nationwide claims data from South Korea.

Methods: This retrospective observational cohort study evaluated the nationwide claims data from the Health Insurance Review and Assessment Services Common Data Model database in Korea. The clinical outcomes between patients with T2DM treated with SGLT2 inhibitor (SGLT2i group) and those treated with DPP4 inhibitor (DPP4i group) added on first-line metformin treatment were compared. Propensity score matching (PSM) was used to ensure the comparability between the groups, and the hazard ratios were calculated using the Cox proportional hazards model. Moreover, the primary outcomes (any new-onset kidney events, acute kidney injury (AKI), chronic kidney disease (CKD), and kidney failure), secondary outcomes (infection, hemodynamic status, and fracture), all-cause mortality, and cardiovascular outcomes were evaluated.

Results: Of the patients, 13,649 were enrolled in the SGLT2i group, while 35,043 were enrolled in the DPP4i group after PSM. The SGLT2i group had a lower risk of kidney outcomes, AKI, and CDK (HR 0.88, 0.61 and 0.74, respectively) than the DPP4i group. For the secondary outcomes, the risk of genital infection was higher, and the risk of hyperkalemia was lower in the SGLT2i group than in the DPP4i group (HR 2.38, and 0.49, respectively). All-cause mortality and cardiovascular outcomes were estimated to be the same as those in previous studies.

Conclusions: We confirmed the SGLT2 inhibitor has a lower risk of new-onset kidney outcomes and chronic kidney disease than the DPP4 inhibitor in patients with T2DM. The SGLT2 inhibitor also showed a high incidence of genital infection and a low incidence of hyperkalemia.