Cost-utility of injectable and oral GLP-1RAs for type 2 diabetes mellitus inadequately controlled with metformin: A Markov model analysis

To evaluate the cost-utility of five glucagon-like peptide-1 receptor agonists (GLP-1RAs), i.e., liraglutide, dulaglutide, polyethylene glycol loxenatide (PEG-loxenatide), and injectable and oral semaglutide, as add-on therapies for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy, from the perspective of the Chinese healthcare system. A Markov model comprising three health states, T2DM without complications, T2DM with complications, and death, was developed using a 1-year cycle length and a 20-year time horizon. Model inputs for glycated hemoglobin (HbA 1c ) reduction were derived from randomized controlled trials published within the preceding five years. Outcomes included direct medical costs, quality-adjusted life years (QALYs), and incremental cost-utility ratios (ICURs). A willingness-to-pay (WTP) threshold equivalent to twice China’s 2024 per capita gross domestic product (GDP) ($26,639.80 per QALY) was applied. One-way and probabilistic sensitivity analyses were conducted to assess parameter uncertainty and robustness of the findings. The ICURs of all injectable GLP-1RAs combined with metformin were below the WTP threshold, indicating favorable cost-utility. The ICURs of injectable semaglutide at doses of 0.25, 0.50, and 1.00 mg were also below China’s 2024 per capita GDP, suggesting particularly favorable economic value. The interventions were ranked by cost-utility as follows: semaglutide (0.50 mg), semaglutide (0.25 mg), semaglutide (1.00 mg), dulaglutide (1.50 mg), liraglutide (0.60 mg), PEG-loxenatide (0.30 mg), oral semaglutide (14 mg), oral semaglutide (25 mg), and oral semaglutide (50 mg). Semaglutide (0.50 mg) had the highest probability of being cost-effective at 77%. In contrast, the ICURs of the oral semaglutide regimens exceeded the WTP threshold, indicating that their additional costs were not economically justified under the model assumptions. Injectable semaglutide combined with metformin appears to be a cost-effective treatment option for patients with T2DM. The economic value of GLP-1RAs varies according to dose and formulation, with injectable formulations demonstrating more favorable cost-utility than oral formulations.