Opening soonNot applicableInterventional
What this study is about
The SMART study is a 96-week, multicenter, randomized, double-blind, placebo-controlled superiority clinical trial. A total of 256 severe obesity patients are randomized 1:1 to either receive the bariatric surgery plus GCG/GLP-1 dual receptor agonist group (receiving sleeve gastrectomy followed by subcutaneous injections of mazdutide weekly, with stepwise dose escalation to a maintenance dose per protocol) or the bariatric surgery plus placebo group (receiving matched procedure plus placebo injections). The primary objective is to evaluate the potential enhancing weight reduction effects of the combination therapy with bariatric surgery and mazdutide measured by the percentage change of excess weight loss.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age18 Years to 70 Years
SexAll
Healthy volunteersNot accepted
ConditionSevere Obesity
Full registry criteria
Inclusion Criteria: * Aged 18-70 years (inclusive), male or female; * BMI≥37.5 kg/m2, with or without obesity-related complications; * Planned to take sleeve gastrectomy * Understand the trial protocol, voluntarily sign the informed consent form (ICF), and agree to follow all study requirements and restrictions. Exclusion Criteria: * Previous gastrointestinal surgery such as stomach and duodenum, or weight loss and metabolic surgery; * History of thyroid C-cell carcinoma, multiple endocrine neoplasia (MEN) 2A or 2B, or relevant family history; * ALT \> 3.0 × ULN (if NAFLD is diagnosed at screening and within 6 months prior to screening, ALT ≤ 5.0 × ULN can be enrolled), or AST \> 3.0 ×ULN, or total bilirubin (TBIL) \> 2 × ULN * Estimated glomerular filtration rate eGFR \< 45 mL/min/1.73 m2 using the CKD-EPI equation * Chronic anemia：Hemoglobin \< 110 g/L (males) or \< 100 g/L (females)； * Have the following 12-lead electrocardiogram (ECGs) abnormalities at screening(\<50 beats/min or \>100 beats/min), 2nd or 3rd degree atrioventricular block, long QT syndrome or QTcF \> 450 ms (males), QTcF \> 470 ms (females), left or right bundle branch block, pre-excitation syndrome, or other significant arrhythmia (except sinus arrhythmia); * Acute hyperglycemic/hypoglycemic events within 1 year, including: diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemic coma, etc; * Participants with previous severe myocardial infarction, stroke, acute and chronic heart failure, cardiac procedure such as percutaneous coronary intervention, coronary artery bypass grafting, or are not suitable for participation in this study after the investigator's assessment; * Previous or confirmed mental illness at screening/randomization phase\[Previous moderate to severe depressionPHQ questionnaire (Depression Screening Scale) ≥ 15 points, C-SSRS questionnaire (Columbia Suicide Severity Scale) category 4 or 5 at screening or randomization, or "Yes" in suicidal behavior or suicidal ideation\]; * Previous specific infectious diseases, incl. acquired immunodeficiency syndrome, viral hepatitis B, viral hepatitis C, etc; * End-stage disease with an expected survival of less than 5 years or previous/current malignancy; * Use of GLP-1 receptor (GLP-1R) agonists or GLP-1R/GCGR agonists or GIPR/GLP-1R agonists or GIPR/GLP-1R/GCGR agonists within three months prior to screening; * History of alcohol or drug abuse at screening; * History of specific drugs use beyond 2 times, incl. moderate anticholinergics, antiparkinsonians, antiepileptic drugs, antipsychotics, benzodiazepines and sedatives, morphine and narcotic analgesics, stimulant drugs, medical marijuana, marijuana, and cannabidiol, etc.; * Pregnant or lactating females, males or females of childbearing potential who are not willing to use contraception throughout the study and for 8 weeks after the end of the study; * Having participated in other clinical investigators who have a conflict of interest with this study; * The investigator suspects that the participant may be allergic to ingredients in the study drug or drugs of the same class;
Treatments and study arms
Sleeve gastrectomy plus early mazdutide initiation
Drug
After sleeve gastrectomy is preformed, mazdutide injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week at 5th month post procedure. The treatment begins with a starting dose of 2.0 mg, followed by a titration schedule increasing by 2.0 mg every 4 weeks (2.0 mg → 4.0 mg). If well-tolerated, participants reached the target maintenance dose of 6.0 mg (4.0 mg → 6.0 mg)weekly for maintenance. The protocol permits adaptive dose downgrade to 4.0 mg weekly when clinically indicated, such as intolerance. The total intervention is maintained until 48 weeks post procedure.
Sleeve gastrectomy followed with early mazdutide placebo initation
Drug
After sleeve gastrectomy is preformed, mazdutide placebo injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week at 5th month post procedure. The treatment begins with a starting dose of 2.0 mg placebo, followed by a titration schedule increasing by 2.0 mg every 4 weeks (2.0 mg → 4.0 mg). If well-tolerated, participants reached the target maintenance dose of 6.0 mg placebo(4.0 mg → 6.0 mg) weekly for maintenance. The protocol permits adaptive dose downgrade to 4.0 mg weekly when clinically indicated, such as intolerance. The total intervention is maintained until 48 weeks post procedure.
