Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report submitted by the manufacturer of semaglutide (Novo Nordisk Pharma, Ltd.) regarding the additional benefits and costeffectiveness of semaglutide plus diet and exercise compared to diet and exercise alone in overweight (body mass index (BMI) of 27 kg/m2 or more) with at least 2 of the weight-related comorbidities including type 2 diabetes or obesity (BMI of 35 kg/m2) with at least 1 of the following weight-related comorbidities: hypertension, dyslipidemia or type 2 diabetes. The patients with overweight or obesity were divided into two groups: those with and without type 2 diabetes. This report summarizes the findings from ATAG's review and re-analysis. The manufacturer presented the patient individual data from the STEP6 trial, a randomized controlled trial in patients with overweight or obesity, to assess the additional benefits of semaglutide plus diet and exercise over diet and exercise alone. Evidence showed that semaglutide plus diet and exercise was associated with a statistically significant reduction in body weight from baseline compared to diet and exercise alone for the two groups based on type 2 diabetes. Similar findings were observed for systolic blood pressure, total cholesterol, and HbA1c in the two groups. Based on the findings, the manufacturer suggested that semaglutide plus diet and exercise had additional benefits compared to diet and exercise alone. The ATAG conducted a systematic review, and identified a total of three trials, consisting of STEP6, STEP1, and STEP2, from the literature. The results of the three trials on the literature were similar to those from STEP6 presented by the manufacturer. The ATAG concluded that semaglutide had additional benefits compared with diet and exercise alone for the patients with overweight or obesity. The manufacturer submitted a cost-effectiveness analysis over a 40-year time horizon using a multi-state Markov model simulating the progression of overweight or obesity with semaglutide plus diet and exercise versus diet and exercise alone. The ATAG identified several challenges with the manufacturer’s analysis. First, the drop-out rates of semaglutide and/or diet and exercise in the manufacturer’s model were based on the studies in Italy and the US. The ATAG used rates based on Japanese data to reflect actual clinical evidence in Japan. Second, the improvement of treatment (diet and exercise) adherence due to early weight loss by semaglutide was sustained after stopping semaglutide. This sustained improvement was considered part of the treatment effects of semaglutide, but was not supported by evidence and the ATAG updated their model to assume that the effect of semaglutide would be disappeared in 1-10 years after stopping semaglutide. Third, the benefits of diet and exercise (e.g., weight loss) at 9 months were maintained throughout life. There is uncertainty around long term effects of diet and exercise. The ATAG assumed that the effects of diet and exercise would disappear in 1-10 years after the first year of treatment. In the ATAG’ base-case analysis, semaglutide plus diet and exercise was associated with more QALYs (incremental QALYs: 0.02 QALYs) and higher costs (incremental costs: JPY 422,553) than diet and exercise alone for patients with overweight or obesity and with type 2 diabetes, leading to an incremental cost-effectiveness ratio (ICER) of JPY 18,216,862/QALY. For patients with overweight or obesity and without type 2 diabetes, the ATAG’ base-case ICER was JPY 13,095,027/QALY (incremental QALYs: 0.03 QALYs, incremental costs: JPY 355,601). In conclusion, for patients with overweight or obesity, the results by the ATAG suggested that the ICERs of semaglutide plus diet and exercise compared to diet and exercise alone were likely to be “more than JPY 10 million per QALY” from the perspective of public healthcare payer in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2306.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com