Effectiveness and Safety of Once-Weekly Semaglutide in Japanese Patients with Type 2 Diabetes: A Retrospective Observational Multicenter Study (ORIGAMI Study).

INTRODUCTION: Once-weekly semaglutide has proven to be a safe and effective treatment for type 2 diabetes; however, clinical trial data on Asian populations are limited, warranting real-world data (RWD). In this study we assessed the effectiveness and safety of semaglutide in Japanese patients with type 2 diabetes using RWD. METHODS: A retrospective analysis was conducted at five diabetes centers in Japan between December 2019 and June 2022. Changes in hemoglobin A1C (HbA1c), body weight (BW), lipid parameters, liver/kidney function, and adverse events were assessed over 52 weeks. Subgroup analyses were stratified by glucagon-like peptide-1 receptor agonist (GLP-1RA)-naïve users versus prior GLP-1RA users (GLP-1RA switch group), baseline body mass index (BMI) (< 30 or ≥ 30 kg/m), and alanine aminotransferase (ALT) level (≤ 30 or > 30 U/L). RESULTS: Of the 503 patients included in the study, 270 (mean age 53 years; 61.8% men; mean duration of diabetes 10.7 years) were included in the per-protocol analysis. Mean (± standard deviation) baseline HbA1c and BMI were 8.1 ± 1.5% and 31.7 ± 6.2 kg/m, respectively; 52% patients were prior GLP-1RA users. HbA1c level had fallen by approximately 0.9% at both 26 and 52 weeks after treatment initiation (p < 0.001), with BW reductions of - 3.2 kg at 26 weeks and - 4.3 kg at 52 weeks (p < 0.001). Lipid profiles and liver function improved significantly (p < 0.001). Compared to prior GLP-1RA users, GLP-1RA-naïve patients showed greater reductions in HbA1c level (- 1.2% vs. - 0.8%, p = 0.009) and BMI (- 1.6 vs. - 1.2 kg/m, p = 0.03). Patients with BMI ≥ 30 kg/mhad a larger reduction in BMI than those with BMI < 30  kg/m(- 1.7 vs. - 1.1 kg/m, p = 0.002), and those with ALT > 30 U/L showed greater HbA1c reduction (- 1.2% vs. - 0.8%, p = 0.04) and improved liver function than those with ALT ≤ 30 U/L. Gastrointestinal adverse events occurred in 53.7% of patients, leading to discontinuation of treatment in 7.6%. CONCLUSIONS: Once-weekly semaglutide improved glycemic control, BW, lipid profiles, and liver function in Japanese patients with type 2 diabetes in RWD and subgroup analyses, supporting a broad effectiveness range. The rate of gastrointestinal adverse events in the RWD was comparable to that in prospective clinical studies. REGISTRATION: University hospital Medical Information Network Clinical Trial Registry No.: UMIN000050499).