Obesity & OverweightPhase 4NCT07657676
Effect of Mazdutide on Coronary Plaque in Patients With Coronary Atherosclerosis and Overweight or Obesity
A Phase 4 study testing Mazdutide in people with Obesity & Overweight and Coronary Heart Disease, run by China National Center for Cardiovascular Diseases at 1 site in China.
Trial summary
This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the effect of mazdutide, a dual GLP-1/GCG receptor agonist, on coronary plaque progression assessed by coronary computed tomography angiography (CCTA) in patients with coronary atherosclerosis and overweight or obesity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity & Overweight, Coronary Heart Disease
- What is being tested?
- Mazdutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- 1 siteChina
- Study dates
- 14 Sep 2026to 31 Dec 2027
- Phase
- Phase 4
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- BMI ≥ 28 kg/m2 or BMI≥ 24kg/m2 with at least one of the following conditions: dyslipidemia, metabolic associated fatty liver disease, hypertension, prediabetes, type 2 diabetes mellitus, or obesity-related obstructive sleep apnea syndrome (at screening or within 6 months prior to screening).
- Coronary stenosis 30-70% confirmed by CAG or CCTA within 3 months prior to enrollment.
- Signed informed consent
- Willing to comply with follow-up
Who cannot join
- History or evidence of the following :
- A history of severe hypoglycemia, or recurrent symptomatic hypoglycemia (≥2 episodes) within the past six months
- Severe heart disease as determined by the investigator, including coronary artery disease that has undergone or is planned for coronary artery bypass grafting or percutaneous coronary intervention, valvular heart disease requiring valve repair or replacement, heart transplantation, severe heart failure (NYHA III-IV) or cardiogenic shock, or a known history of left ventricular ejection fraction ≤30%
- A hemorrhagic/ischemic stroke or transient ischemic attack within six months prior to screening
- A history of acute or chronic pancreatitis, gallbladder/bile duct disease, or pancreatic injury
- Presence of severe diseases such as malignant tumors, lymphoma, liver cirrhosis, HIV-positive status, etc., with an expected survival of less than 2 years
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- Contraindications to GLP-1/GCG dual receptor agonists, such as hypersensitivity or severe intolerance
- A personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Use of the following medications or treatments prior to screening :
- Use of weight-affecting medications (e.g., systemic steroids, tricyclic antidepressants, psychiatric/sedative medications, etc.) within three months prior to screening
- Use of GLP-1 RA or GIP/GLP-1 RA (exposure to investigational drugs) within three months prior to screening
- Participation in other clinical trials (exposure to investigational drugs) within three months prior to screening
- Known clinically significant abnormal gastric emptying or current use of medications that directly affect gastrointestinal motility
- Laboratory test results meeting any of the following criteria at screening (repeat testing within one week is permitted if there is a clear reason, and the reason for retesting must be documented by the investigator)
- Serum calcitonin ≥50 ng/L (pg/mL)
- ALT/AST >3.0 × ULN
- eGFR <30 mL/min/1.73m²
- Abnormal thyroid function (TSH >6 mIU/L or <0.4 mIU/L)
- Pregnancy, planned pregnancy, or breastfeeding
- Contraindications to CCTA, including severe allergy to iodine contrast agents, presence of cardiac implantable electronic devices or other metal implants that may affect image analysis
- Inability to complete the study or comply with study requirements as determined by the investigator Exclusion criteria for the PET-CT substudy: All exclusion criteria of the main study, as well as contraindications to PET-CT examination
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100037
Xiao Wang, MD, 86-10-88396953, wangxiao@fuwai.com
Luo Fang, 86-10-88396953, luofang@fuwaihospital.org
About this study
Official title: Effect of Mazdutide on Coronary Plaque Progression in Patients With Coronary Atherosclerosis and Overweight or Obesity: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial
This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the effect of mazdutide, a dual GLP-1/GCG receptor agonist, on coronary plaque progression assessed by coronary computed tomography angiography (CCTA) in patients with coronary atherosclerosis and overweight or obesity. The primary endpoint is the change in total non-calcified plaque volume (NCPV) from baseline to week 52. Secondary endpoints include changes in pericoronary adipose tissue inflammation (fat attenuation index, FAI), plaque composition, metabolic parameters, inflammatory biomarkers, and clinical outcomes. A substudy will include 18F-NaF PET/CT imaging.
Read the detailed description
Coronary atherosclerosis is the principal pathological substrate underlying most cardiovascular events and remains a leading cause of morbidity and mortality. Overweight and obesity are well-established independent risk factors that drive the development and progression of coronary atherosclerotic plaque, and thus represent critical modifiable targets for therapeutic intervention.
Prior studies have shown that GLP-1 receptor agonists (GLP-1RAs) provide hypoglycemic, weight-loss, and cardiovascular protective benefits. Mazdutide, the first approved GLP-1/GCG dual receptor agonist, combines GLP-1-mediated insulin secretion and appetite suppression with GCG-driven energy expenditure. Phase III trials have demonstrated robust glycemic and weight benefits, along with reductions in hs-CRP and liver fat. Given that dual-receptor activation yields more robust metabolic improvements than single-receptor agonism, mazdutide may possess greater potential than GLP-1 monotherapy in suppressing coronary plaque progression.
Therefore, we propose a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of 52 weeks of Mazdutide treatment on CCTA-assessed non-calcified plaque volume (NCPV) in patients with coronary atherosclerosis and overweight or obesity.
PET-CT substudy: A subset of eligible patients will be enrolled into a sub-study, we aim to evaluate the efficacy of Mazdutide on plaque inflammation assessed by 18F-NaF PET/CT.
- Conditions
- Obesity & Overweight, Coronary Heart Disease
- Being tested
- Mazdutide, Placebo
- Keywords
- GLP-1RA, CCTA, Mazdutide, Obesity, Plaque, Overweight, Coronary Heart Disease
- Medical subject headings
- Obesity, Overweight, Coronary Disease, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MazdutideDrug
Mazdutide administered subcutaneously once weekly, starting at 2 mg for 4 weeks, then escalated to 4 mg for 4 weeks, and then to 6 mg thereafter until week 52.
PlaceboDrug
Placebo administered subcutaneously once weekly, starting at 2 mg for 4 weeks, then escalated to 4 mg for 4 weeks, and then to 6 mg thereafter until week 52.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Mazdutide | Experimental | Not described Receives: Drug: Mazdutide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in total non-calcified plaque volume (NCPV) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Secondary outcomes (28)
Change in RCA pericoronary fat attenuation index (RCA-FAI) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in LAD pericoronary fat attenuation index (LAD-FAI) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in LCX pericoronary fat attenuation index (LCX-FAI) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in lesion pericoronary fat attenuation index (lesion-FAI) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in total plaque volume (TPV) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in percent atheroma volume (PAV) by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in low-attenuation plaque volumes by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in fibrous plaque volumes by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in fibrofatty plaque volumes by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in calcified plaque volumes by CCTA from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in total cholesterol from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in triglycerides from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in LDL-C from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in non-HDL-C from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in ApoB from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in HbA1c from baseline to 52 weeks
Measured: Baseline and 52 weeks
Changein fasting glucose from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in uric acid from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in Lp(a) from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in hs-CRP from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in IL-6 from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in TNF-α from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in body weight from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in waist circumference from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in waist-to-hip ratio from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in SBP from baseline to 52 weeks
Measured: Baseline and 52 weeks
Change in DBP from baseline to 52 weeks
Measured: Baseline and 52 weeks
Incidence of major adverse cardiovascular events (MACE) at 52 weeks
Measured: Baseline and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2026
- Study start14 Sep 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity & OverweightStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China National Center for Cardiovascular Diseases
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Xiao Wang, China National Center for Cardiovascular Diseases
- Investigators
- Ke fei Dou, Principal investigator, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeXiao Wang, Principal investigator, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07657676
- Sponsor's protocol ID
- 2026-3068
- Status last verified
- Oct 2026
- First submitted
- 14 Jun 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No