Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity

NCT07135141 | Not Yet Recruiting

• 1 other identifier: SMART trial
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Severe Obesity

Outcome Measures

Primary Outcomes (1)

• the rate of excess weight loss(EWL%) compared to baseline

  EWL%=\[preoperative weight-post operative weight\]/\[preoperative weight -ideal body weight\]x100%, ideal weight=height²(m²)x25kg/m²

  At 48th week post procedure

Secondary Outcomes (14)

• Assessing the change in BMI(kilogram/square meter, kg/m²） classification compared to baseline(Based on the BMI classification in Chinese adiposity diagnosis and treatment guideline 2024)

  At 48th week post procedure

• Assessing the rate of total body weight loss(TBWL%) compared to baseline

  At 48th week post procedure

• Assessing the change of waist circumference(centimeter, cm) compared to baseline

  at 48th week post procedure

• Assessing the change of hip circumference(centimeter, cm) compared to baseline

  At 48th week post procedure

• Assessing the change of blood pressure(incl. systolic blood pressure and diastolic blood pressure) compared to baseline（Hydrargyrum, mmHg）

  At 48th week post procedure

Study Arms (2)

Sleeve gastrectomy plus mazdutide group

EXPERIMENTAL

Participants will receive weekly subcutaneous injections of mazdutide at 5th month post sleeve gastrectomy(starting at 2.0 mg, with stepwise dose escalation to a target maintenance dose of 6.0 mg and optional adaptive downgrade to 4.0 mg if necessary)

Drug: Sleeve gastrectomy plus early mazdutide initiation

Sleeve gastrectomy plus mazdutide placebo group

PLACEBO COMPARATOR

Participants will receive weekly subcutaneous injections of matched placebo at 5th month post sleeve gastrectomy

Drug: Sleeve gastrectomy followed with early mazdutide placebo initation

Interventions

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 plus mazdutide group

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.

Sleeve gastrectomy plus mazdutide placebo group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.;

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (14)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Location

Beijing Hospital

Beijing, China

Location

Peking University People's Unviersity

Beijing, China

Location

The Third Hospital of Central South University

Changsha, China

Location

West China Hospital of Sichuan University

Chengdu, China

Location

The First Affiliated Hospital of Jinan University(Guangzhou Overseas Chinese Hospital)

Guangzhou, China

Location

Qilu Hospital of Shandong University

Jinan, China

Location

Kunming First People's Hospital

Kunming, China

Location

Nanjing Drum Tower Hospital

Nanjing, China

Location

Huadong Hospital affiliated to Fudan University

Shanghai, China

Location

Shanghai Sixth People's Hospital to Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, China

Location

Tianjin Medical University General Hospital

Tianjing, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, China

Location

MeSH Terms

Conditions

Obesity, Morbid

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

ZhongTao Zhang, MD, PhD

CONTACT

+86 010 63139361; zhangzht@ccmu.edu.cn

Mengyi Li, MD, PhD

CONTACT

+86 010 63139361; limengyi@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Vice president of hospital

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 21, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2029
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

CN (14)