近日，美国芝加哥大小Liana K Billings团队研究了Eloralintide作为一种治疗肥胖的选择性胰淀素受体激动剂的疗效与安全性。相关论文于2025年11月6日发表在《柳叶刀》杂志上。

以胰淀素为基础的治疗方法正在成为有前景的肥胖药物。Eloralintide是一种新型的，选择性的amylin受体激动剂，正在开发用于体重管理。研究组进行了一项2期、双盲、随机、安慰剂对照试验，目的是在肥胖或超重且至少有一种体重相关合并症的成年人中，评估Eloralintide与安慰剂的一系列剂量和剂量递增方案的有效性和安全性。

研究组从美国46个研究中心招募了263名参与者。年龄在18-75岁，BMI为30 kg/m²或更高，或BMI为27 kg/m²或更高，且至少有一种体重相关合并症且无2型糖尿病的患者被随机分配（2:1:1:1:2:1:2），接受每周一次皮下注射安慰剂或Eloralintide，剂量分别为1mg、3mg、6mg或9mg，或剂量递增至6 - 9mg或3 - 9mg，持续48周。主要终点是治疗48周后体重从基线变化的百分比。疗效分析包括所有随机分配的参与者，安全性分析包括所有随机分配并接受至少一剂研究治疗的参与者。

在2024年2月5日至2025年8月14日期间，263名参与者（平均年龄49.0岁[SE 12.6]，平均体重109.1 kg[22.8]，体重指数39.1 kg/m2[6.8]， 204名[78%]女性，205名[78%]白人）被随机分配到接受Eloralintide（1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6 - 9 mg, n=24; 3 - 9 mg, n=52）或安慰剂（n=53）。疗效分析是基于随机分配的263名参与者。48周后体重与基线的平均百分比变化（疗效估计）为-9% (1 mg， 95% CI为- 12.6至- 6.3),-12% (3 mg, - 14.9至- 9.8),-18% (6 mg, - 20.7至- 14.5),-20% (9 mg, - 22.7至- 17.5),-20% （6 -9 mg, - 22.7至- 17.0）和-16% (3 -9 mg, - 18.6至- 14.1)，而安慰剂组为- 0.4%（- 2.2至1.4）。Eloralintide最常见的不良事件是恶心（1mg 11%, 3mg 13%, 6mg 64%, 9mg 33%, 6 - 9mg 54%, 3 - 9mg 25%，安慰剂14%）和疲劳（1mg 0%, 3mg 13%, 6mg 29%, 9mg 43%, 6 - 9mg 46%, 3 - 9mg 21%，安慰剂12%）。

研究结果表明，Eloralintide在48周内产生了具有临床意义的剂量依赖性的体重减轻，并且通常耐受性良好，支持Eloralintide用于肥胖治疗的潜在用途。

附：英文原文

Title: Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial

Author: Liana K Billings, Stanley Hsia, Harold Bays, Beth Tidemann-Miller, Jessica O’Hagan, Lai San Tham, Annabelle Butler, Christof Kazda, Kieren J Mather, Tamer Coskun

Issue&Volume: 2025-11-06

Abstract:

Background

Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity.

Methods

We enrolled 263 participants from 46 research centres in the USA. Individuals aged 18–75 years with a BMI of 30 kg/m2 or higher, or a BMI of 27 kg/m2 or higher with at least one weight-related comorbidity and without type 2 diabetes were randomly assigned (2:1:1:1:2:1:2) to receive once-per-week subcutaneous injections of placebo or eloralintide at 1 mg, 3 mg, 6 mg, or 9 mg, or dose escalations of 6–9 mg or 3–9 mg for 48 weeks. The primary endpoint was percent change in bodyweight from baseline after 48 weeks of treatment. Efficacy analyses included all randomly assigned participants, and safety analyses included all participants who were randomly assigned and received at least one dose of study treatment. This study was completed on Aug 14, 2025, and is registered with ClinicalTrials.gov (NCT06230523).

Findings

Between Feb 5, 2024, and Aug 14, 2025, 263 participants (mean age 49·0 years [SE 12·6], mean bodyweight 109·1 kg [22·8], BMI 39·1 kg/m2 [6·8], 204 [78%] female, and 205 [78%] White) were randomly assigned to receive eloralintide (1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6–9 mg, n=24; and 3–9 mg, n=52) or placebo (n=53). The efficacy analyses were based on the 263 participants randomly assigned. The mean percent change in bodyweight from baseline after 48 weeks (efficacy estimand) was –9% (1 mg, 95% CI –12·6 to –6·3), –12% (3 mg, –14·9 to –9·8), –18% (6 mg, –20·7 to –14·5), –20% (9 mg, –22·7 to –17·5), –20% (6–9 mg, –22·7 to –17·0), and –16% (3–9 mg, –18·6 to –14·1), compared with –0·4% (–2·2 to 1·4) in the placebo group. The most common adverse events with eloralintide were nausea (1 mg 11%, 3 mg 13%, 6 mg 64%, 9 mg 33%, 6–9 mg 54%, 3–9 mg 25%, and placebo 14%) and fatigue (1 mg 0%, 3 mg 13%, 6 mg 29%, 9 mg 43%, 6–9 mg 46%, 3–9 mg 21%, and placebo 12%).

Interpretation

Eloralintide produced clinically meaningful, dose-dependent reductions in bodyweight over 48 weeks and was generally well tolerated, supporting eloralintide's potential use for obesity treatment.

DOI: 10.1016/S0140-6736(25)02155-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02155-5/abstract