Long-Term Effectiveness and Cost-Effectiveness of Metformin Combined with Liraglutide or Exenatide for Type 2 Diabetes Mellitus Based on the CORE Diabetes Model Study

Background
Type 2 diabetes mellitus (T2DM) is associated with β cell impairment. Agonists of the glucagon-like peptide 1 (GLP-1) receptor (such as liraglutide and exenatide) can increase the number of pancreatic β cells and improve cell function. These drugs contribute to the long-term control of T2DM.
Objective
To evaluate the cost-effectiveness of metformin combined with liraglutide or exenatide in Chinese patient with T2DM.
Methods
Patients with T2DM from the Third Hospital of Hebei Medical University were treated with oral metformin combined with liraglutide (0.6 mg/day, could be increased by 0.6 mg weekly until 1.2 or 1.8 mg) or exenatide (5 μg bid for four weeks, increased to 10 μg bid). The computer simulation model CORE was used to calculate the 30-year expected life expectancy, quality-adjusted life years (QALY), direct costs, HbA1c levels, body mass index (BMI), and the incidence of cardiovascular, renal, and ocular complications of T2DM. Patients were followed up for 52 weeks. Medication costs were calculated according to retail prices in China. A 3% annual discount was adopted in this study.
Results
The 30-year simulation showed that the total direct medical costs were lower using liraglutide compared to exenatide by 2130 RMB/QALY yearly, while the expected life expectancy and QALY were increased by 0.471 years and 0.388, respectively, using liraglutide with an incremental cost-effectiveness of -11,550 RMB/QALYs.
Conclusion
Liraglutide 1.2 mg/day was superior to exenatide 10 μg bid with respect to cost-effectiveness in Chinese patients with T2DM.

**背景**
2型糖尿病（Type 2 diabetes mellitus, T2DM）与胰岛β细胞功能损伤密切相关。胰高糖素样肽-1（glucagon-like peptide 1, GLP-1）受体激动剂（如利拉鲁肽（liraglutide）与艾塞那肽（exenatide））可增加胰腺β细胞数量并改善细胞功能，此类药物有助于实现2型糖尿病的长期血糖控制。

**研究目的**
本研究旨在评估二甲双胍（metformin）联合利拉鲁肽或艾塞那肽用于中国2型糖尿病患者的成本效益。

**研究方法**
本研究纳入河北医科大学第三医院的2型糖尿病患者，予以口服二甲双胍联合利拉鲁肽（初始剂量0.6 mg/日，可每周递增0.6 mg，直至剂量达1.2 mg或1.8 mg），或联合艾塞那肽（初始剂量5 μg 每日2次，持续4周后增量至10 μg 每日2次）治疗。采用计算机模拟模型CORE（CORE）计算患者30年预期寿命、质量调整寿命年（quality-adjusted life years, QALY）、直接医疗成本、糖化血红蛋白（HbA1c）水平、体质量指数（body mass index, BMI）以及2型糖尿病相关心血管、肾脏及眼部并发症的发生率。对患者进行为期52周的随访。药物成本按照中国国内零售价格进行核算。本研究采用3%的年度贴现率。

**研究结果**
30年模拟结果显示，与艾塞那肽方案相比，利拉鲁肽方案的年度总直接医疗成本降低2130元/质量调整寿命年；同时利拉鲁肽方案可使患者预期寿命延长0.471年，质量调整寿命年提升0.388，增量成本效益比为-11550元/质量调整寿命年。

**研究结论**
在中国2型糖尿病患者中，1.2 mg/日剂量的利拉鲁肽联合二甲双胍方案在成本效益方面优于10 μg每日2次剂量的艾塞那肽联合二甲双胍方案。