Dutta Deep, Nagendra Lakshmi, Anne Beatrice, Kumar Manoj, Sharma Meha, Kamrul-Hasan A B M
Department of Endocrinology CEDAR Superspeciality Healthcare New Delhi India.
Department of Endocrinology, JSS medical college JSS Academy of Higher Education and Research Mysore India.
Obes Sci Pract. 2024 Feb 26;10(2):e743. doi: 10.1002/osp4.743. eCollection 2024 Apr.
Orforglipron is a novel once-daily oral non-peptide glucagon-like peptide-1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta-analysis has analyzed the efficacy and safety of orforglipron; this meta-analysis aimed to address this knowledge gap.
A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight.
From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow-up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD -5.48%, 95% CI [-7.64, -3.33], < 0.01), 24 mg/day (MD -8.51%, 95% confidence interval (CI) [-9.88, -7.14], < 0.01), 36 mg/day (MD -8.84%, 95% CI [-11.68, -6.00], < 0.01) and 45 mg/day (MD -8.24%, 95% CI [-12.84, -3.63], < 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side-effects were predominant side effects, being dose-dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones.
Orforglipron at 24-45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24-36 mg/day is the most optimal dose for orforglipron as an anti-obesity medicine.
奥佛利司他是一种新型的每日一次口服非肽类胰高血糖素样肽-1受体激动剂，近期有多项随机对照试验（RCT）评估了其在糖尿病和肥胖症治疗中的作用。尚无荟萃分析对奥佛利司他的疗效和安全性进行分析；本荟萃分析旨在填补这一知识空白。
在电子数据库中进行系统检索，以识别纳入接受奥佛利司他治疗的肥胖个体并与安慰剂或活性对照进行比较的RCT。主要关注的结局是体重变化百分比。
从最初筛选的12篇文章中，分析了3项涉及774人的RCT数据，随访时间长达36周。与安慰剂相比，接受12毫克/天奥佛利司他的患者（平均差值（MD），MD -5.48%，95%置信区间（CI）[-7.64，-3.33]，P<0.01）、24毫克/天（MD -8.51%，95%置信区间（CI）[-9.88，-7.14]，P<0.01）、36毫克/天（MD -8.84%，95% CI [-11.68，-6.00]，P<0.01）和45毫克/天（MD -8.24%，95% CI [-12.84，-3.63]，P<0.01）的体重减轻百分比显著更高。与基线相比，能够实现体重减轻>15%的患者百分比在24毫克/天奥佛利司他组显著更高[优势比（OR）21.90（95% CI [4.06，118.15]，P = 0.0003）、36毫克/天（OR 17.43，95% CI [3.18，95.66]，P = 0.001）和45毫克/天（OR 23.17，95% CI [4.37，123.03]，P = 0.0002）。与安慰剂相比，所有剂量的奥佛利司他的总不良事件（但非严重不良事件）显著更高，且剂量越高，风险比越高。胃肠道副作用是主要副作用，呈剂量依赖性，恶心、呕吐、便秘和胃食管反流是主要的副作用。
24 - 45毫克/天剂量的奥佛利司他是一种有效的减肥药物。疗效与副作用情况表明，24 - 36毫克/天是奥佛利司他作为抗肥胖药物的最适宜剂量。
