Capel Margarita, Ciudin Andreea, Mareque María, Rodríguez-Rincón Raquel María, Simón Susana, Oyagüez Itziar
AstraZeneca, Madrid, Spain.
Hospital Universitari Vall d´Hebron, Barcelona, Spain.
Pharmacoecon Open. 2020 Jun;4(2):277-286. doi: 10.1007/s41669-019-0171-y.
The aim of this study was to assess the efficiency of exenatide 2 mg/week compared with other glucagon-like peptide-1 (GLP-1) receptor agonists (dulaglutide 1.5 mg/week, liraglutide 1.2 mg/day, liraglutide 1.8 mg/day and lixisenatide 20 μg/day) in adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin alone from the perspective of the Spanish National Health System (NHS).
Quality-adjusted life-years (QALYs) gained and total costs of each assessed drug combined with metformin (2 g/day) were estimated over a 40-year time horizon using the Cardiff Diabetes Model (based on UK Prospective Diabetes Study [UKPDS] 68 equations), which simulates disease progression considering the T2DM-related micro- and macrovascular complications, hypoglycaemia, nausea, body mass index (BMI) changes and treatment discontinuation due to adverse effects (AEs). Drug efficacy derived from an indirect comparison performed in a network meta-analysis. Patient characteristics were obtained from the literature. The baseline utility value (0.80) was derived from the PANORAMA study, applying utility decrements to micro- and macrovascular complications, hypoglycaemia episodes and changes in BMI. Treatment discontinuation due to AEs or poorly controlled diabetes (HbA1c > 7.5%) involved switching to second-line (basal insulin) or third-line (basal-bolus insulin) treatment. Total cost (€, 2018) included the costs of drug acquisition, hypoglycaemia, weight gain, micro- and macrovascular complications, nausea and treatment discontinuation due to AEs. An annual discount rate of 3% was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (SA) were performed.
In base-case, exenatide 2 mg/week resulted in more QALYs (8.26) than dulaglutide 1.5 mg/week (8.19 QALYs), liraglutide 1.2 mg/day (8.10 QALYs), liraglutide 1.8 mg/day (8.20 QALYs) and lixisenatide 20 μg/day (8.13 QALYs). Total cost/patient was €20,423.27 (exenatide 2 mg/week), €22,611.94 (dulaglutide 1.5 mg/week), €21,065.97 (liraglutide 1.2 mg/day), €24,865.69 (liraglutide 1.8 mg/day) and €21,334.58 (lixisenatide 20 μg/day). Deterministic SA confirmed the robustness of the model. In the probabilistic SA, 95-99% of the 1000 Monte Carlo iterations performed were under a hypothetical willingness-to-pay threshold of €20,000/QALY gained.
Exenatide 2 mg/week would be a dominant strategy (more effective and less costly) versus the other GLP-1 receptor agonists assessed for the treatment of T2DM patients who are not adequately controlled on metformin alone.
本研究旨在从西班牙国家卫生系统（NHS）的角度，评估与其他胰高血糖素样肽-1（GLP-1）受体激动剂（度拉鲁肽1.5毫克/周、利拉鲁肽1.2毫克/天、利拉鲁肽1.8毫克/天和利司那肽20微克/天）相比，2毫克/周的艾塞那肽对单用二甲双胍血糖控制不佳的2型糖尿病（T2DM）成年患者的疗效。
使用卡迪夫糖尿病模型（基于英国前瞻性糖尿病研究[UKPDS]68方程），在40年的时间范围内估计每种评估药物与二甲双胍（2克/天）联合使用所获得的质量调整生命年（QALY）和总成本，该模型在考虑T2DM相关微血管和大血管并发症、低血糖、恶心、体重指数（BMI）变化以及因不良反应（AE）导致的治疗中断的情况下模拟疾病进展。药物疗效来自网络荟萃分析中的间接比较。患者特征从文献中获取。基线效用值（0.80）来自全景研究，对微血管和大血管并发症、低血糖发作和BMI变化应用效用递减。因AE或糖尿病控制不佳（糖化血红蛋白>7.5%）导致的治疗中断涉及改用二线（基础胰岛素）或三线（基础-餐时胰岛素）治疗。总成本（欧元，2018年）包括药物采购、低血糖、体重增加、微血管和大血管并发症、恶心以及因AE导致的治疗中断的成本。对成本和结果应用3%的年贴现率。进行了确定性和概率敏感性分析（SA）。
在基础病例中，2毫克/周的艾塞那肽比1.5毫克/周的度拉鲁肽（8.19个QALY）、1.2毫克/天的利拉鲁肽（8.10个QALY）、1.8毫克/天的利拉鲁肽（8.20个QALY）和20微克/天的利司那肽（8.13个QALY）产生更多的QALY（8.26）。每位患者的总成本为20423.27欧元（2毫克/周的艾塞那肽）、22611.94欧元（1.5毫克/周的度拉鲁肽）、21065.97欧元（1.2毫克/天的利拉鲁肽）、24865.69欧元（1.8毫克/天的利拉鲁肽）和21334.58欧元（20微克/天的利司那肽）。确定性SA证实了模型的稳健性。在概率SA中，所进行的1000次蒙特卡洛迭代中有95%-99%低于假设的每获得一个QALY支付意愿阈值20000欧元。
对于单用二甲双胍血糖控制不佳的T2DM患者，与其他评估的GLP-1受体激动剂相比，2毫克/周的艾塞那肽将是一种占优策略（更有效且成本更低）。
