Comparative Effectiveness of Once-Weekly Semaglutide Versus Sulfonylureas, DPP4 Inhibitors, and Thiazolidinediones in Patients with Type 2 Diabetes and Chronic Kidney Disease.

INTRODUCTION

Once-weekly (OW) semaglutide has shown renal benefits in clinical trials for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study compared clinical outcomes between OW semaglutide and selected oral glucose-lowering medications in real-world settings.

METHODS

Adults with T2D and CKD were identified from the Optum's de-identified Clinformatics® Data Mart Database (01/01/2016-06/30/2023). Two samples were included: patients ineligible for or with suboptimal response to sodium-glucose cotransporter type 2 inhibitor (SGLT2i) (sample 1) and patients meeting the eligibility criteria for renal outcome analysis [sample 2; no estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73 m2 during the 6 months before the index date and no evidence of dialysis, kidney transplantation, or kidney failure at baseline]. In sample 1, glycated hemoglobin (HbA1c), eGFR, body weight, and systolic blood pressure (SBP) were described and compared using linear mixed-effects models. In sample 2, composite renal outcome consisting of dialysis, kidney transplantation, sustained eGFR < 15 mL/min/1.73 m2, or all-cause death, was evaluated and compared using Cox proportional hazard model.

RESULTS

Using model-based estimates at 12 months, OW semaglutide was associated with greater reductions in HbA1c (- 0.54%), body weight (- 6.69 kg), SBP (- 3.63 mmHg), and greater improvement in eGFR (2.06 mL/min/1.73 m2) compared to controls (all P < 0.05), with effects largely sustained during follow-up. Moreover, OW semaglutide was associated with a significantly lower risk of the composite renal outcome (adjusted hazard ratio = 0.78, 95% confidence interval: 0.62, 0.99).

CONCLUSIONS

In real-world practice, OW semaglutide has been associated with sustained benefits in glycemic control, eGFR improvement, weight loss, and SBP reduction over selected oral glucose-lowering medications among patients with T2D and CKD who were ineligible for or with suboptimal response to SGLT2i. It has also been associated with a reduced risk of the composite renal outcome in patients meeting the eligibility criteria for the renal outcome analysis.