Obesity is a chronic, progressive, and relapsing disease. Although lifestyle interventions and anti-obesity medications are effective for inducing weight loss, evidence regarding their role in long-term weight maintenance after pharmacologically induced weight reduction remains limited. In addition, the high cost and potential adverse effects of weight-loss medications restrict their prolonged use, and it is unclear whether low dose medication, intensive life style intervention or together can serve as an effective strategy for weight maintenance.

This randomized controlled trial aims to evaluate the effectiveness of a 1-year intensive lifestyle intervention, a reduced dose of mazdutide (3.0 mg once weekly), or their combination in weight maintenance among individuals with obesity who have achieved initial weight loss after intensive treatment with high dose mazdutide. The study seeks to provide high-quality clinical evidence to inform long-term weight maintenance strategies after weight loss in patients with obesity.

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.

All IPD that underlie results in a publication.

After publication.

IPD and supporting information will be avaible to researchers upon reasonable request (e.g. with a practical and meaningful research proposal).