Introduction The objective of the current study was to assess the long-term cost-effectiveness of once-weekly semaglutide 0.5 mg and 1.0 mg versus dulaglutide 1.5 mg for the treatment of patients with type 2 diabetes uncontrolled on metformin in the Chinese setting. Methods The Swedish Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to evaluate the long-term health and economic outcomes of once-weekly semaglutide and dulaglutide. Analysis was conducted from the perspective of the Chinese healthcare systems over a time horizon of 40 years. Data on baseline cohort characteristics and treatment effects were sourced from the SUSTAIN 7 clinical trial. Costs included treatment costs and costs of complications. Projected health and economic outcomes were discounted at a rate of 5% annually. The robustness of the results was evaluated through one-way sensitivity analyses and probabilistic sensitivity analyses. Results Compared with dulaglutide 1.5 mg, once-weekly semaglutide 0.5 mg and 1.0 mg were associated with improvements in discounted life expectancy of 0.04 and 0.10 years, respectively, and improvements in discounted quality-adjusted life expectancy of 0.08 and 0.19 quality-adjusted life years (QALYs), respectively. Clinical benefits were achieved at reduced costs, with lifetime cost savings of 8355 Chinese Yuan (CNY) with once-weekly semaglutide 0.5 mg and 11,553 CNY with once-weekly semaglutide 1.0 mg. Sensitivity analyses verified the robustness of the research results. Conclusions Once-weekly semaglutide was suggested to be dominant (more effective and less costly) versus dulaglutide 1.5 mg in patients with type 2 diabetes uncontrolled on metformin treatment in China.