Current partner codePEPTIDESDE
NCT07135141·Not applicable·INTERVENTIONAL

Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity

Status

Not yet recruiting

Phase

Not applicable

Enrollment

256

Locations

14

Results

Not posted

Publications

0

Study summary

What the protocol is testing.

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.

Interventions

Treatment arms and agents.

DRUG

Sleeve gastrectomy plus early mazdutide initiation

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.

DRUG

Sleeve gastrectomy followed with early mazdutide placebo initation

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.

Timeline

From registration to results.

  1. First posted

    Aug 21, 2025

  2. Study start

    Sep 30, 2025

  3. Primary completion

    Sep 30, 2027

  4. Study completion

    Sep 30, 2029

  5. Results posted

    Not reported

  6. Registry updated

    Aug 21, 2025

Outcomes

What the study measures.

Primary outcomes

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

Time frame · At 48th week post procedure

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

Secondary outcomes

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)

Time frame · At 48th week post procedure

BMI classification in China: BMI 18.5-24 kg/m² healthy; 24\<BMI\<28 kg/m² overweight, 28\<BMI\<32.5 kg/m² mild obesity, 32.5\<BMI\<37.5 kg/m² moderately obese, BMI\>37.5 kg/m² severe or extremely severe obesity

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

Time frame · At 48th week post procedure

Total body weight loss (TBWL) is the pre-op weight minus the post op body weight

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

Time frame · at 48th week post procedure

waist circumference is measured with centimeter(cm)

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

Time frame · At 48th week post procedure

Hip circumference is measured with centimeter(cm).

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

Time frame · At 48th week post procedure

Blood pressure is measured with mmHg.

Assessing the percentage change(%) of body fat or fat-free mass compared to baseline

Time frame · At 48th week post procedure

Body fat or fat-free mass is measured by dual energy X-ray absorptiometry(DEXA)

Assessing the percentage change(%) of liver fat content or pancreatic fat content compared to baseline

Time frame · At 48th week post procedure

Liver fat content or pancreatic fat content is measured with Magnetic resonance imaging-derived proton density fat fraction(MRI-PDFF)

Assessing the percentage change(%) of triglyceride(TG), low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC) or high-density lipoprotein cholesterol(HDL-C) compared to baseline

Time frame · At 48th week post procedure

TG(millimoles per liter, mmol/L) , LDL-C(millimoles per liter, mmol/L) ,TC(millimoles per liter, mmol/L) or HDL-C(millimoles per liter, mmol/L) is tested in the lab of study sites with local standards according to Chinese Guidelines for Lipid Management

Assessing the change of aspartate transaminase(AST) or alanine aminotransferase(ALT) compared to baseline

Time frame · At 48th week post procedure

Assessing the change(%) of serum uric acid compared to baseline

Time frame · At 48th week post procedure

serum uric acid(micromoles per liter, µmol/L) is tested in the lab of study sites according to Chinese National Standards

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
70 Years
Sex
ALL
Healthy volunteers
No

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;

Study locations

14 registered sites.

China. Showing up to 24 locations stored in the fast local snapshot.

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Beijing Hospital

Beijing, China

Peking University People's Unviersity

Beijing, China

The Third Hospital of Central South University

Changsha, China

West China Hospital of Sichuan University

Chengdu, China

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

Guangzhou, China

Qilu Hospital of Shandong University

Jinan, China

Kunming First People's Hospital

Kunming, China

Nanjing Drum Tower Hospital

Nanjing, China

Huadong Hospital affiliated to Fudan University

Shanghai, China

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

Shanghai, China

The Second Hospital of Hebei Medical University

Shijiazhuang, China

Tianjin Medical University General Hospital

Tianjing, China

Zhongnan Hospital of Wuhan University

Wuhan, China

Publications

Results and literature.

No PMID-linked publications were present in this registry snapshot.

Primary links

Continue at the source.

Related trials

More studies on Mazdutide.

Related PeptideStat pages

Put the record in context.

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