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

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. 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. 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). 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. Once-weekly semaglutide has been approved by the United States Food and Drug Administration to reduce the risk of worsening kidney function and cardiovascular death in patients with type 2 diabetes and chronic kidney disease . This study evaluated the comparative effectiveness of OW semaglutide versus selected oral glucose-lowering medications in patients with type 2 diabetes and chronic kidney disease. Optum’s de-identified Clinformatics® Data Mart Database was used to select patients ineligible for or with suboptimal response to sodium–glucose cotransporter type 2 inhibitor (sample 1) and patients without reduced eGFR or kidney failure (sample 2). In sample 1, patients treated with once-weekly semaglutide had better reductions in blood glucose, body weight, systolic blood pressure, and greater improvement in kidney function at 12 months after treatment initiation, and these effects were largely sustained during follow-up. In sample 2, once-weekly semaglutide users had a significantly lower risk of the composite renal outcome consisting of dialysis, kidney transplantation, sustained kidney impairment, or death. This real-world study suggests that once-weekly semaglutide is a promising treatment option and supports the real-world effectiveness of once-weekly semaglutide in managing type 2 diabetes and chronic kidney disease.