262-OR: Pemvidutide, a GLP-1/Glucagon Dual Receptor Agonist, in Subjects with Overweight or Obesity—A 48-Week, Placebo-Controlled, Phase 2 (MOMENTUM) Trial

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2024-06-23 DOI:10.2337/db24-262-or

LOUIS ARONNE, M. SCOTT HARRIS, M S. ROBERTS, JOHN J. SUSCHAK, SHAHEEN TOMAH, JONATHAN KASPER, LIANG HE, JAY YANG, JUAN P. FRIAS, SARAH K. BROWNE

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引用次数: 0

Abstract

Introduction & Objective: Pemvidutide is a GLP-1/glucagon dual receptor agonist in development for treatment of obesity. Methods: MOMENTUM was a Phase 2, randomized, placebo-controlled trial of subjects with overweight (BMI 27.0-29.9 kg/m2) and at least one obesity-related comorbidity or obesity (BMI >30.0 kg/m2) randomized 1:1:1:1 to pemvidutide (1.2, 1.8, 2.4 mg) or placebo administered subcutaneously weekly for 48 weeks. Results: A total of 391 subjects with mean age, body weight, and BMI of 50 yrs, 105 kg, and 37 kg/m2 were enrolled. At week 48, subjects receiving pemvidutide achieved mean weight losses of 10.3%, 11.2%, and 15.6% at the 1.2 mg, 1.8 mg, and 2.4 mg doses vs. placebo (2.2%), respectively (p<0.001 vs. placebo, all doses, Figure 1), with 51.8% and 32.1% of subjects at the 2.4 mg dose level achieving ≥15% and ≥20% weight loss and 48% of subjects having resolution of baseline obesity by trial conclusion. Subjects with elevated serum lipids at baseline had reductions of up to 55.8%, 20.0%, and 21.8% in triglycerides, total cholesterol and LDL at week 48. Most adverse events were mild to moderate with only 1 drug-related SAE; glycemic control (glucose, HbA1c) was maintained with minimal increases in heart rate. Conclusion: Pemvidutide was safe and well-tolerated and significantly reduced body weight and serum lipids over 48 weeks of treatment. Disclosure L. Aronne: Advisory Panel; Novo Nordisk. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Altimmune Inc. Consultant; Lilly Diabetes. Advisory Panel; Pfizer Inc. Consultant; UnitedHealth Group. Advisory Panel; Boehringer-Ingelheim. Board Member; AstraZeneca. Advisory Panel; Amgen Inc. M. Harris: Employee; Altimmune Inc. M.S. Roberts: Employee; Altimmune Inc. J.J. Suschak: Employee; Altimmune Inc. S. Tomah: Employee; Altimmune Inc. J. Kasper: Employee; Altimmune Inc. L. He: None. J. Yang: None. J.P. Frias: Research Support; Akero Therapeutics, Inc. Consultant; Akero Therapeutics, Inc. Research Support; Altimmune Inc. Consultant; Altimmune Inc. Research Support; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; 89bio, Inc. Consultant; 89bio, Inc. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Merck & Co., Inc. Consultant; Merck & Co., Inc. Research Support; Novartis Pharmaceuticals Corporation. Consultant; Novartis Pharmaceuticals Corporation, Novo Nordisk. Board Member; Novo Nordisk. Research Support; Novo Nordisk, Pfizer Inc. Consultant; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Stock/Shareholder; Biomea Fusion, Inc. Employee; Biomea Fusion, Inc. S.K. Browne: Employee; Altimmune Inc.

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262-OR： GLP-1/胰高血糖素双受体激动剂培美度肽治疗超重或肥胖症--一项为期 48 周、安慰剂对照的 2 期（MOMENTUM）试验

引言和目的：培伐度肽是一种 GLP-1/胰高血糖素双重受体激动剂，目前正在开发用于治疗肥胖症。研究方法MOMENTUM是一项2期随机安慰剂对照试验，受试者体重超重（体重指数为27.0-29.9 kg/m2）且至少有一种肥胖相关合并症或肥胖（体重指数为30.0 kg/m2），受试者按1:1:1:1的比例随机接受培美度肽（1.2、1.8、2.4 mg）或安慰剂治疗，每周皮下注射48周。研究结果共有 391 名受试者参加了研究，他们的平均年龄、体重和 BMI 分别为 50 岁、105 公斤和 37 公斤/平方米。第48周时，与安慰剂（2.2%）相比，服用1.2毫克、1.8毫克和2.4毫克剂量的受试者平均体重分别下降了10.3%、11.2%和15.6%（与安慰剂相比，所有剂量的p<0.001，图1），其中服用2.4毫克剂量的受试者中分别有51.8%和32.1%的人体重下降了≥15%和≥20%，48%的受试者在试验结束时消除了基线肥胖。基线血脂升高的受试者在第48周时甘油三酯、总胆固醇和低密度脂蛋白分别降低了55.8%、20.0%和21.8%。大多数不良反应为轻度至中度，只有 1 例与药物相关的 SAE；血糖控制（葡萄糖、HbA1c）得以维持，心率增加幅度很小。结论培伐度肽安全且耐受性良好，在48周的治疗中能显著降低体重和血清脂质。披露 L. Aronne：顾问团；诺和诺德公司。顾问；诺和诺德公司。顾问团；礼来糖尿病公司、Altimmune 公司。顾问；礼来糖尿病公司。顾问团；辉瑞公司顾问；联合健康集团。顾问团；勃林格殷格翰公司。董事会成员；阿斯利康公司。安进公司顾问团成员M. Harris：雇员；Altimmune Inc.M.S. Roberts：员工；Altimmune Inc.J.J. Suschak：员工；Altimmune Inc.S. 托马Altimmune 公司员工J. 卡斯帕：Altimmune 公司员工L. He：无。J. Yang：无。J.P. Frias：研究支持；Akero Therapeutics, Inc.顾问；Akero Therapeutics, Inc.研究支持；Altimmune Inc.顾问；Altimmune Inc.研究支持；Boehringer-Ingelheim.顾问；Boehringer-Ingelheim.研究支持；89bio, Inc.顾问；89bio, Inc.研究支持；礼来公司。礼来公司顾问团Speaker's Bureau; Eli Lilly and Company.研究支持；Merck & Co.顾问；Merck & Co.研究支持；诺华制药公司。诺华制药公司、诺和诺德公司顾问。诺和诺德公司董事会成员。研究支持；诺和诺德公司、辉瑞公司。辉瑞公司顾问赛诺菲顾问团赛诺菲发言人办公室。研究支持；赛诺菲股票/股东；Biomea Fusion, Inc.员工；Biomea Fusion, Inc.S.K. Browne：Altimmune Inc.雇员。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.