Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215 , in adults with overweight or obesity: Results from a phase 1 randomized clinical trial
Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215 , in adults with overweight or obesity: Results from a phase 1 randomized clinical trial
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胰高血糖素样肽 1/胰高血糖素受体共激动剂 G3215 的适应性输注，用于超重或肥胖的成人：1 期随机临床试验的结果
DOI：
10.1111/dom.15448
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Hope D
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文献类型：
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作者：
Hope D
目的 确定连续输注胰高血糖素样肽受体 (GLP-1R)/胰高血糖素受体 (GCGR) 共激动剂 G3215 对于超重或肥胖的成人是否安全且耐受性良好。方法在超重或肥胖受试者（无论是否患有 2 型糖尿病）中进行 G3215 的 1 期随机、双盲、安慰剂对照试验 结果 招募了 26 名参与者并随机分配，其中 23 名完成了为期 14 天的 G3215 或安慰剂皮下输注。最常见的不良事件是恶心或呕吐，大多数情况下这些不良事件都很轻微，可以通过实时调整药物输注来缓解。 G3215 输注没有心血管问题。药代动力学特征与连续输注超过 14 天一致。输注 G3215 14 天后，最小二乘平均体重减轻 2.39 公斤，而安慰剂输注则为 0.84 公斤（p < 0.05）。在接受 G3215 的参与者中还观察到食物消耗减少，并且血糖没有恶化。在 G3215 治疗的参与者中观察到血脂状况得到改善，并且与 GCGR 激活一致，在输注期间观察到循环氨基酸广泛减少。结论 GLP-1/GCGR 共激动剂 G3215 的适应性连续输注是安全的且耐受性良好，提供了控制药物暴露的独特策略。通过允许快速、以反应为导向的滴定，该策略可以减轻不良反应，并在比目前每周使用 GLP-1R 和多激动剂更短的时间内实现显着的体重减轻。这些结果支持 G3215 用于治疗肥胖和代谢疾病的持续开发。
AimsTo determine whether a continuous infusion of a glucagon‐like peptide receptor (GLP‐1R)/glucagon receptor (GCGR) co‐agonist, G3215 is safe and well tolerated in adults with overweight or obesity.MethodsA phase 1 randomized, double blind, placebo‐controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes.ResultsTwenty‐six participants were recruited and randomized with 23 completing a 14‐day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real‐time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least‐squares mean body weight loss of 2.39 kg was achieved with a 14‐day infusion of G3215, compared with 0.84 kg with placebo infusion (p< .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215‐treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period.ConclusionAn adaptive continuous infusion of the GLP‐1/GCGR co‐agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response‐directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP‐1R and multi‐agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.