Three-year changes in renal function after switching from injectable GLP-1 receptor agonists to oral semaglutide in Japanese patients with type 2 diabetes: a retrospective cohort study.

BACKGROUND: While the FLOW trial established the renoprotective effects of subcutaneous semaglutide, real-world evidence regarding the long-term renal effects of therapeutic switching from injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) to oral semaglutide remains limited. We evaluated long-term changes in renal function following this therapeutic switch. METHODS: This retrospective cohort study included 36 patients with type 2 diabetes (T2D) who were switched from liraglutide or dulaglutide to oral semaglutide (7 mg/day). Changes in the urinary albumin-to-creatinine ratio (UACR) and annual estimated glomerular filtration rate (eGFR) slope were compared between the 3-year periods immediately before and after the switch. RESULTS: Three years after switching, the median UACR significantly decreased from 54.3 to 35.8 mg/g creatinine ( < 0.05). The annual eGFR slope improved from - 1.92 (95% CI - 2.66 to - 1.18) before switching to - 0.26 (95% CI - 1.01 to 0.50) mL/min/1.73 m/year after switching (difference: 1.67; < 0.01). Subgroup analysis showed a significant improvement in eGFR slope among patients with baseline eGFR ≥ 60 mL/min/1.73 m(difference: 1.85; < 0.01). Reductions in glycated hemoglobin (- 0.33%, < 0.05) and body weight (- 3.50 kg, < 0.01) were sustained at 3 years. Improvement in eGFR slope was significantly associated with the magnitude of weight loss ( < 0.05) and lower baseline HbA1c ( < 0.01). CONCLUSIONS: Therapeutic switching from injectable GLP-1RAs to oral semaglutide was associated with attenuation of renal function decline and reduction in albuminuria over 3 years. These findings suggest potential long-term renal benefits of oral semaglutide in routine clinical practice.