Severe ObesitySMARTNCT07135141
Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity
A study testing Sleeve gastrectomy plus early mazdutide initiation in people with Severe Obesity, run by Beijing Friendship Hospital at 14 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Severe Obesity
- What is being tested?
- Sleeve gastrectomy plus early mazdutide initiation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 256 participants
- Where
- 14 sitesChina
- Study dates
- 30 Sep 2025to 30 Sep 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 18Show fewer
- 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;
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
China14 sites
Beijing Friendship Hospital, Capital Medical University
Beijing
Beijing Hospital
Beijing
Lixing Guo, +86 13901317569, glx1218@163.com
Lixin Guo
Peking University People's Unviersity
Beijing
Linong Li, MD,PhD, +86 010 63139361, jiln@bjmu.edu.cn
Zhaohui Zhong, +86 13691102568, zhongzhaohui@pkuph.edu.cn
The Third Hospital of Central South University
Changsha
Liyong Zhu, +86 19373109453, zly8128@csu.edu.cn
Liyong Zhu
West China Hospital of Sichuan University
Chengdu
Yi Chen, +86 13881823928
Yi Chen
The First Affiliated Hospital of Jinan University(Guangzhou Overseas Chinese Hospital)
Guangzhou
Jingge Yang, +86 13560099502, dukeyjg@126.com
Jingge Yang
Qilu Hospital of Shandong University
Jinan
Shaozhuang Liu, +86 18560085165, liushaozhuang@sdu.edu.cn
Shaozhuang Liu
Kunming First People's Hospital
Kunming
JianHui Yin, +86 15877990129, 1551389142@qq.com
Jianhui Yin
Nanjing Drum Tower Hospital
Nanjing
Xitai Sun, +86 13815424927, sunxitai@hotmail.com
Xitai Sun
Huadong Hospital affiliated to Fudan University
Shanghai
Yan Gu, +86 13661756660, yangu@fudan.edu.cn
Yan Gu
Shanghai Sixth People's Hospital to Shanghai Jiao Tong University School of Medicine
Shanghai
Jianzhong Di, +86 18930177207, dijianzhong@163.com
Jianzhong Di
The Second Hospital of Hebei Medical University
Shijiazhuang
Tao Li, +86 13930483525, litao18353@163.com
Tao Li
Tianjin Medical University General Hospital
Tianjing
Xiaoyu Liang, +86 13802036941, liangxiaoyu2025@hotmail.com
Xiaoyu Liang
Zhongnan Hospital of Wuhan University
Wuhan
Zhen Li, +86 15071396243, kamei_li@163.com
Zhen Li
About this study
Official title: Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity:A Multicenter, Randomized, Double-Blind, Placebo-Controlled Superiority Trial
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
- Being tested
- Sleeve gastrectomy plus early mazdutide initiation, Sleeve gastrectomy followed with early mazdutide placebo initation
- Medical subject headings
- Obesity, Morbid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleeve gastrectomy plus early mazdutide initiationDrug
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 initationDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: Drug: Sleeve gastrectomy followed with early mazdutide placebo initation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
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
Measured: At 48th week post procedure
Assessing the rate of total body weight loss(TBWL%) compared to baseline
Total body weight loss (TBWL) is the pre-op weight minus the post op body weight
Measured: At 48th week post procedure
Assessing the change of waist circumference(centimeter, cm) compared to baseline
waist circumference is measured with centimeter(cm)
Measured: at 48th week post procedure
Assessing the change of hip circumference(centimeter, cm) compared to baseline
Hip circumference is measured with centimeter(cm).
Measured: At 48th week post procedure
Assessing the change of blood pressure(incl. systolic blood pressure and diastolic blood pressure) compared to baseline（Hydrargyrum, mmHg）
Blood pressure is measured with mmHg.
Measured: At 48th week post procedure
Assessing the percentage change（%） of body fat or fat-free mass compared to baseline
Body fat or fat-free mass is measured by dual energy X-ray absorptiometry(DEXA)
Measured: At 48th week post procedure
Assessing the percentage change（%） of liver fat content or pancreatic fat content compared to baseline
Liver fat content or pancreatic fat content is measured with Magnetic resonance imaging-derived proton density fat fraction(MRI-PDFF)
Measured: At 48th week post procedure
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
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
Measured: At 48th week post procedure
Assessing the change of aspartate transaminase(AST) or alanine aminotransferase(ALT) compared to baseline
Measured: At 48th week post procedure
Assessing the change(%) of serum uric acid compared to baseline
serum uric acid(micromoles per liter, µmol/L) is tested in the lab of study sites according to Chinese National Standards
Measured: At 48th week post procedure
Assessing the change of nutrition status (incl. albumin, victamin B12, folic acid or serum iron and so forth) compared to baseline
Albumin(gram per liter, g/L), folic acid(nanomoles per liter,nmol/L), Victamin B12(picomole per liter, pmol/L), serum iron(milligrams per liter, mg/L) is tested in the lab of study sites according to Chinese National Standards
Measured: At 48th week post procedure
Assessing the change of body weight related life quality(IWQOL-Lite) , upper GI symptom scale(GERDQ) or overall life quality scale(SF-36) compared to baseline
IWQOL-Lite Score ranges among 31-105, the higher the score, the poorer the quality of life; When GerdQ score ≥8 points, it means the risk of gastroesophageal reflux is high; SF-36 score includes 8 dimensions, and the total score equals mean transformed scores of 8 dimensions, the higher the score, the higher the quality of life, transformed score of each dimension=［（actual score-the lowest possible score）/general average possible score］×100
Measured: At 48th week post procedure
Assessing the rate(%) of procedure-related or drug-related complications, re-admission, or major cardiovascular adverse events
Procedure-related complications include gastroesophageal reflux disease, malnutrition and so on; Drug-related complications include nausea, vomiting, diarrhea and so on
Measured: At 48th week post procedure
Assessing the rate(%) of body weight regain among participants
'Body weight rebounded over 15% compared to nadir weight' is referred to as weight regain
Measured: At 96th week post procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2025
- Study start30 Sep 2025 (estimated)
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Friendship Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhongtao Zhang, Beijing Friendship Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07135141
- Sponsor's protocol ID
- SMART trial
- Acronym
- SMART
- Status last verified
- Aug 2025
- First submitted
- 12 Aug 2025
- Last updated
- 21 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes