ASCEND-1: Lifestyle Intervention Plus Mazdutide for Weight Management

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.