Ferrara Francesco, Bazzani Denise, Crivelli Barbara, Danieli Elisa, Gazzola Pietro, Guarnieri Greta, Handschin Giulia, Lauria Claudia, Marchetti Carlotta, Sbraga Emanuele, Zero Carmen, Zovi Andrea, Langella Roberto, Parati Chiara
Pharmaceutical Department, Asl Napoli 3 Sud, Dell' Amicizia Street 72, Nola, Naples, Italy.
Pharmaceutical Department, ATS Val Padana via Dei Toscani 1, 46100, Mantua, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 14. doi: 10.1007/s00210-025-04319-0.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, have emerged as effective therapies for glycaemic control and weight reduction in type 2 diabetes and obesity. Both injectable and oral formulations have been investigated in large phase III clinical trials, with growing interest in their long-term efficacy and safety. To review and compare the efficacy, safety, and tolerability of injectable and oral semaglutide formulations, with a focus on their role in chronic weight and glycaemic management. A narrative review was conducted based on data from pivotal clinical trials and real-world studies. Efficacy outcomes included changes in body weight and glycated haemoglobin (HbA1c). Safety profiles, adverse events, and patient adherence factors were also assessed. Injectable semaglutide (2.4 mg weekly) showed a mean weight reduction of 14.9% over 68 weeks in the STEP 1 trial, compared to 15.1% with oral semaglutide (50 mg daily) in the OASIS 1 study. Both formulations demonstrated significant improvements in HbA1c and cardiometabolic parameters. A real-world study found comparable efficacy between formulations. Gastrointestinal adverse events were most common, while serious events were rare. Long-term use was essential for sustained weight loss, as discontinuation led to significant weight regain. No consistent associations with increased cancer or psychiatric adverse events were confirmed. Both oral and injectable semaglutide are effective and generally well-tolerated options for chronic management of type 2 diabetes and obesity. Treatment adherence, long-term safety, and cost considerations should guide therapeutic choices. Ongoing monitoring is warranted to optimize outcomes and minimize risks.
胰高血糖素样肽-1受体激动剂（GLP-1RAs），包括司美格鲁肽，已成为2型糖尿病和肥胖症患者血糖控制和体重减轻的有效治疗方法。注射剂和口服制剂均已在大型III期临床试验中进行了研究，人们对其长期疗效和安全性的兴趣与日俱增。旨在回顾和比较注射用和口服司美格鲁肽制剂的疗效、安全性和耐受性，重点关注它们在慢性体重和血糖管理中的作用。基于关键临床试验和真实世界研究的数据进行了叙述性综述。疗效结果包括体重和糖化血红蛋白（HbA1c）的变化。还评估了安全性概况、不良事件和患者依从性因素。在STEP 1试验中，注射用司美格鲁肽（每周2.4毫克）在68周内平均体重减轻了14.9%，而在OASIS 1研究中，口服司美格鲁肽（每日50毫克）的平均体重减轻了15.1%。两种制剂在HbA1c和心脏代谢参数方面均有显著改善。一项真实世界研究发现两种制剂的疗效相当。胃肠道不良事件最为常见，而严重事件很少见。长期使用对于持续减重至关重要，因为停药会导致体重显著反弹。未证实与癌症或精神科不良事件增加存在一致关联。口服和注射用司美格鲁肽都是2型糖尿病和肥胖症慢性管理的有效且耐受性良好的选择。治疗依从性、长期安全性和成本考量应指导治疗选择。需要持续监测以优化治疗效果并将风险降至最低。
