Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report submitted by the manufacturer of tirzepatide (Eli Lilly Japan K.K.) regarding the additional benefits and cost-effectiveness of tirzepatide plus diet and exercise (tirzepatide) compared with semaglutide plus diet and exercise (semaglutide) in patients having either hypertension, dyslipidemia, or type 2 diabetes, with overweight (body mass index (BMI) of 27 kg/m2 or more) with at least 2 of the weight-related comorbidities or with obesity (BMI of 35 kg/m2 or more) (as of March 2025). This report summarizes the findings of the ATAG review and re-analysis. To assess the additional benefits of tirzepatide over semaglutide, the manufacturer conducted indirect comparisons because there were no appropriate randomized controlled trial (RCT) comparing tirzepatide and semaglutide. Evidence has shown that tirzepatide was associated with a statistically significant reduction in body weight from baseline compared with semaglutide. Similar findings were observed for HbA1c levels. Based on these findings, the manufacturer suggested that tirzepatide has additional benefits compared with semaglutide. The ATAG conducted a systematic review and identified an RCT comparing tirzepatide with semaglutide (SURMOUNT-5 trial, which enrolled patients with overweight or obesity without type 2 diabetes), which the manufacturer also identified. The SURMOUNT-5 trial showed that tirzepatide was associated with a statistically significant reduction in body weight from baseline compared with semaglutide, but there were several concerns, such as flexible maximum doses and dose duration. The ATAG accepted the manufacturer's explanation and concluded that tirzepatide had additional benefits compared with semaglutide for patients with overweight or obesity.The manufacturer submitted a cost-effectiveness analysis using a patient-level model simulating the progression of overweight or obesity for tirzepatide and semaglutide. The ATAG identified several issues in the manufacturer's analysis. First, the maximum dose of tirzepatide in the manufacturer's model was 10 mg. The results of database analysis by ATAG focusing on the distribution of the maximum doses of tirzepatide using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) revealed that its maximum dose was more than 10 mg for more than half of the patients. The ATAG estimated the cost-effectiveness results for tirzepatide at maximum doses of 5 mg, 10 mg, and 15 mg, and combined the results based on the dose usage proportions. Second, the baseline proportion of patients with type 2 diabetes in the manufacturer's analysis was not based on real-world data; thus, the ATAG conducted an NDB analysis to estimate the proportion, and conducted a reanalysis using the results. Third, the manufacturer adopted quality of life (QOL) values derived from the general Japanese population using a vignette study. The ATAG considered that the utility values obtained from the vignette study may underestimate those of obesity patients, and decided that it was more appropriate to use the QOL values obtained from patients with overweight or obesity in an RCT comparing semaglutide with diet and exercise alone (STEP1 trial). Fourth, the manufacturer's analysis indicated a difference in the incidence of obstructive sleep apnea (OSA) between tirzepatide and semaglutide treatment groups. Because the difference was not supported by clinical trials or literature, the ATAG assumed no difference in the incidence of OSA.In the ATAG's base-case analysis, tirzepatide was associated with more quality-adjusted life years (QALYs) (incremental QALYs: 0.028 QALYs) and higher costs (incremental costs: JPY 4,845) than semaglutide for patients with overweight or obesity, leading to an incremental cost-effectiveness ratio (ICER) of JPY 171,201/QALY. In conclusion, for patients with overweight or obesity, the results by the ATAG suggested that the ICERs of tirzepatide compared to semaglutide were likely to be "less than JPY 2 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: 2026

URL for published report: https://c2h.niph.go.jp/en/results/C2H2410.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