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.