Lifestyle program plus low-dose mazdutide to keep weight off

Achieving Sustained Weight Control Via Exercise, Nutrition & Drugs (Mazdutide) (ASCEND- 1 Trial)

This study tests whether a year of intensive lifestyle changes, once-weekly low-dose mazdutide (3.0 mg), or both can help adults with obesity maintain weight loss achieved with high-dose mazdutide.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 420 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Locations: 13 sites (Chongqing, Chongqing Municipality and 12 other locations)
• Trial ID: NCT07517042 on ClinicalTrials.gov

What this trial studies

This randomized controlled trial enrolls adults with obesity who have achieved initial weight loss after intensive high-dose mazdutide treatment and randomizes them to one year of intensive lifestyle intervention, reduced-dose mazdutide (3.0 mg once weekly), or the combination. The primary focus is on weight maintenance over 12 months following initial pharmacologic-induced weight reduction. The trial is conducted at several major hospitals in China and includes regular clinic visits and lifestyle counseling sessions alongside medication as assigned. Results aim to inform practical strategies for sustaining weight loss while addressing cost and safety concerns of long-term medication use.

Who should consider this trial

Good fit: Adults aged 18 years or older with BMI 28.0–45.0 kg/m² who have already lost weight after intensive high-dose mazdutide treatment and can attend study visits and provide informed consent.

Not a fit: Patients with secondary causes of obesity or serious exclusions—such as recent myocardial infarction or stroke, severe liver or kidney impairment, active serious infections, or recent gastrointestinal surgery—are unlikely to be eligible or to benefit from the tested strategies.

Why it matters

Potential benefit: If successful, it could identify ways to keep weight off long-term while reducing medication dose, side effects, and cost.

How similar studies have performed: Similar GLP-1 receptor agonists have produced strong initial weight loss in prior trials, but high-quality evidence on long-term maintenance after dose reduction or combined intensive lifestyle support remains limited.

Eligibility criteria

Inclusion Criteria:

* Adult men or women aged 18 years or older;
* Simple obesity, defined as a body mass index (BMI) of 28.0-45.0 kg/m²;
* Able and willing to provide written informed consent.

Exclusion Criteria:

* Active pulmonary tuberculosis, malignant tumors, human immunodeficiency virus (HIV) infection, or other serious infectious or systemic diseases;
* Severe hepatic impairment (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \>3 times the upper limit of normal), severe renal impairment, or end-stage renal disease (estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m²);
* Severe cardiovascular diseases, including angina pectoris, myocardial infarction, or stroke within the past 6 months;
* Severe gastrointestinal diseases, or a history of gastrointestinal resection surgery within the past year;
* Acute or chronic pancreatitis, gallbladder disease, or pancreatic injury;
* Obesity secondary to other causes, including Cushing's syndrome, primary hypothyroidism, hypothalamic obesity, or acromegaly; drug-induced obesity, such as obesity related to the use of antipsychotic agents or glucocorticoids;
* Current smoker or habitual smoking within the past 3 months;
* Current use of other weight-loss medications or a history of bariatric surgery;
* Previously diagnosed diabetes mellitus or current use of glucose-lowering medications;
* Pregnant or breastfeeding women, or women planning pregnancy during the study period;
* Inability to complete a 2-year follow-up due to health conditions, relocation, or other reasons;
* Any other condition deemed by the investigator to make the participant unsuitable for participation in the study.

Where this trial is running

Chongqing, Chongqing Municipality and 12 other locations

• The Second Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Recruiting)
• Fujian Provincial Hospital, Affiliated to Fuzhou University — Fuzhou, Fujian, China (Recruiting)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Recruiting)
• Zhongnan Hospital of Wuhan University — Wuhan, Hubei, China (Recruiting)
• Nanjing First Hospital, Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)
• The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University — Suzhou, Jiangsu, China (Recruiting)
• Huadong Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanghai Tenth People's Hospital, School of Medicine, Tongji University — Shanghai, Shanghai Municipality, China (Recruiting)
• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
• The Affiliated Hospital of Southwest Medical University — Luzhou, Sichuan, China (Recruiting)
• Zhejiang Provincial People's Hospital — Hangzhou, Zhejiang, China (Recruiting)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: JINGJING JIANG, MD, PhD

Conditions Obesity; Weight Control; obesity; GLP-1 RA; Exercise; Nutrition; Sustained weight Control