Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial.

We assessed the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with obesity or overweight and at least one weight-related condition without diabetes.

我们评估了在没有糖尿病的肥胖或超重参与者中，elecoglipron 与安慰剂相比在疗效、安全性和耐受性方面的效果，这些参与者至少有一种与体重相关的状况。

Methods

In this double-blind, randomised, controlled, phase 2 dose-ranging study with a total treatment duration of 36 weeks, adult participants were recruited from medical research centres and hospitals in Australia, Canada, Germany, Japan, Taiwan, the UK, and the USA.

在这项为期36周的双盲、随机、对照的2期剂量范围研究中，成年参与者从澳大利亚、加拿大、德国、日本、台湾、英国和美国的医学研究中心和医院招募。

Participants were aged 18 years or older living with obesity (BMI ≥30 kg/m2) or with overweight (BMI ≥27 kg/m2) with at least one weight-related condition and without type 2 diabetes.

参与者年龄在18岁或以上，患有肥胖症（BMI ≥30 kg/m2）或超重（BMI ≥27 kg/m2），至少有一种与体重相关的疾病，且没有2型糖尿病。

Eligible participants were randomly assigned in a 2:3:3:3:3:5 ratio to receive 5 mg, 15 mg, 50 mg, 75 mg (weekly titration), or 75 mg (every 2-week titration) of elecoglipron or matching placebo.

符合条件的参与者按2:3:3:3:3:5的比例随机分配，接受5 mg、15 mg、50 mg、75 mg（每周递增）或75 mg（每两周递增）的elecoglipron或相应的安慰剂治疗。

Elecoglipron was administered as oral once-daily tablets without titration (5 mg and 15 mg) and as three different dose-titration regimens.

Elecoglipron以口服每日一次的片剂形式给予，无需递增（5 mg和15 mg），并以三种不同的剂量递增方案进行。

The daily dose of 50 mg was evaluated using an every-4-weeks dose-escalation schedule, while 75 mg was assessed with weekly or every 2-week dose-escalation schedules.

使用每4周一次的剂量递增计划评估了每日50毫克剂量，而75毫克剂量则通过每周或每两周一次的剂量递增计划进行评估。

Participants, treating physicians, and sponsor were masked to the treatment allocation.

参与者、治疗医生和赞助方对治疗分配情况进行了盲法处理。

The dual primary endpoints were percent change in bodyweight from baseline and the proportion of patients reaching at least 5% weight loss at week 26.

主要终点是基线体重百分比变化和第26周达到至少5%体重减轻的患者比例。

Safety and tolerability were assessed in all participants who received at least one dose of study treatment.

在所有接受至少一次研究治疗剂量的参与者中评估了安全性和耐受性。

This trial is registered at ClinicalTrials.gov (NCT06579092) and is completed.

该试验已在ClinicalTrials.gov注册（NCT06579092），并已完成。

Results

From Oct 8, 2024, to Feb 18, 2025, 472 individuals were screened for potential study inclusion, 162 did not meet the inclusion criteria, and 310 participants were randomly assigned to the varied elecoglipron groups or placebo. 288 participants (93%) completed the study and 231 (75%) completed the assigned treatment.

从2024年10月8日至2025年2月18日，共有472名个体接受了潜在研究纳入的筛查，其中162人未满足纳入标准，310名参与者被随机分配到不同的elecoglipron组或安慰剂组。288名参与者（占93%）完成了研究，231名（占75%）完成了分配的治疗。

The mean age of participants was 48·4 years (SD 13·7), 225 (73%) were female, 85 (27%) were male, their mean bodyweight was 106·9 kg (SD 24·1), and their mean BMI was 38·2 kg/m2 (SD 7·2).

参与者的平均年龄为48.4岁（标准差13.7），225人（73%）为女性，85人（27%）为男性，平均体重为106.9公斤（标准差24.1），平均体质指数（BMI）为38.2 kg/m²（标准差7.2）。

At week 26, the estimated mean change from baseline in bodyweight was between -2·6% (5 mg elecoglipron), and -10·5% (75 mg with weekly titration steps) compared with -0·6% with placebo.

在第26周时，与基线相比，体重的估计平均变化范围为-2.6%（5毫克elecoglipron）至-10.5%（75毫克，每周调整剂量），而安慰剂组为-0.6%。

The estimated proportion of participants reaching weight reductions of at least 5% at week 26 was 40·4-88·8% with elecoglipron versus 15·6% with placebo.

在第26周时，使用elecoglipron的参与者中估计有40.4-88.8%的人体重至少减轻了5%，而使用安慰剂的参与者中这一比例为15.6%。

Adverse events were reported by 84% (27 of 32) to 98% (48 of 49) of participants across elecoglipron doses compared with 84% (68 of 81) in the placebo group, the most common being nausea, constipation, diarrhoea, headache, and vomiting.

在不同剂量的elecoglipron组中，有84%（32人中的27人）至98%（49人中的48人）的参与者报告了不良事件，与之相比，安慰剂组中有84%（81人中的68人）报告了不良事件，最常见的不良事件包括恶心、便秘、腹泻、头痛和呕吐。

interpretation

Daily oral elecoglipron demonstrated clinically meaningful weight reductions and a safety and tolerability profile consistent with the GLP-1 receptor agonist class in this phase 2 dose-ranging study, supporting phase 3 investigation in people living with obesity or overweight.

在这项II期剂量范围研究中，每日口服elecoglipron显示出具有临床意义的减重效果，并且其安全性和耐受性特征与GLP-1受体激动剂类药物一致，支持在肥胖或超重人群中进行III期研究。

funding

AstraZeneca.

阿斯利康。