Current partner codePEPTIDESDE
NCT07657676·Phase 4·INTERVENTIONAL

Effect of Mazdutide on Coronary Plaque in Patients With Coronary Atherosclerosis and Overweight or Obesity

Status

Not yet recruiting

Phase

Phase 4

Enrollment

116

Locations

1

Results

Not posted

Publications

0

Study summary

What the protocol is testing.

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.

Full detailed description

Obesity prevalence has risen sharply, making elevated BMI a leading cause of global mortality and disability. Excess adiposity drives inflammation and coronary heart disease, highlighting an urgent need for effective pharmacological interventions to achieve sustained weight loss and reduce residual cardiovascular risk. Non-calcified plaques represent a key high-risk feature for cardiovascular events. Inflammation serves as a key mechanism in the initiation and progression of non-calcified plaques. Furthermore, pericoronary adipose tissue (PCAT) attenuation, a non-invasive imaging biomarker of inflammation, demonstrates a significant positive correlation with non-calcified plaque burden (r = 0.55, P \< 0.001). Individuals with baseline PCAT attenuation ≥ -75 Hounsfield units (HU) exhibit a three-fold increased risk of non-calcified plaque progression. GLP-1RAs could offer hypoglycemic, weight-loss, and cardiovascular protective benefits. The mechanisms underlying their cardiovascular advantages are partially understood: beyond improving lipid metabolism and reducing blood glucose, they exert vascular protective effects by inhibiting systemic inflammatory responses and modulating the secretory function of PVAT. For instance, liraglutide has been shown to improve vascular endothelial function by reducing apoB levels, while semaglutide reduces epicardial adipose tissue volume. Animal studies show glucagon (GCG) has distinct anti-inflammatory mechanisms from GLP-1. 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 demonstrate robust glycemic and weight benefits, plus reduced hs-CRP and liver fat. Thus, Mazdutide may offer superior potential over GLP-1 monotherapy in mitigating coronary plaque progression and inflammation. 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 assessed by 18NaF PET/CT.

Interventions

Treatment arms and agents.

DRUG

Mazdutide

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.

DRUG

Placebo

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.

Timeline

From registration to results.

  1. First posted

    Jun 18, 2026

  2. Study start

    May 25, 2026

  3. Primary completion

    Oct 31, 2027

  4. Study completion

    Feb 28, 2028

  5. Results posted

    Not reported

  6. Registry updated

    Jun 18, 2026

Outcomes

What the study measures.

Primary outcomes

Change from baseline in total non-calcified plaque volume (NCPV) at 52 weeks measured by CCTA

Time frame · 52 weeks

Secondary outcomes

Change from baseline in RCA pericoronary fat attenuation index (RCA-FAI) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in LAD pericoronary fat attenuation index (LAD-FAI) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in LCX pericoronary fat attenuation index (LCX-FAI) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in lesion pericoronary fat attenuation index (lesion-FAI) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in total plaque volume (TPV) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in percent atheroma volume (PAV) at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in low-attenuation plaque volumes at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in fibrous plaque volumes at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in fibrofatty plaque volumes at 52 weeks by CCTA

Time frame · 52 weeks

Change from baseline in calcified plaque volumes at 52 weeks by CCTA

Time frame · 52 weeks

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: 1. Age ≥ 18 years 2. 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). 3. Coronary stenosis 30-70% confirmed by CAG or CCTA 4. Signed informed consent 5. Willing to comply with follow-up Exclusion Criteria: 1. History or evidence of the following : 1. A history of severe hypoglycemia, or recurrent symptomatic hypoglycemia (≥2 episodes) within the past six months 2. 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% 3. A hemorrhagic/ischemic stroke or transient ischemic attack within six months prior to screening 4. A history of acute or chronic pancreatitis, gallbladder/bile duct disease, or pancreatic injury 5. Presence of severe diseases such as malignant tumors, lymphoma, liver cirrhosis, HIV-positive status, etc., with an expected survival of less than 2 years 6. Contraindications to GLP-1/GCG dual receptor agonists, such as hypersensitivity or severe intolerance 7. A personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 2. Use of the following medications or treatments prior to screening : 1. Use of weight-affecting medications (e.g., systemic steroids, tricyclic antidepressants, psychiatric/sedative medications, etc.) within three months prior to screening 2. Use of GLP-1 RA or GIP/GLP-1 RA (exposure to investigational drugs) within three months prior to screening 3. Participation in other clinical trials (exposure to investigational drugs) within three months prior to screening 4. Known clinically significant abnormal gastric emptying or current use of medications that directly affect gastrointestinal motility 3. 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) 1. Serum calcitonin ≥50 ng/L (pg/mL) 2. ALT/AST \>3.0 × ULN 3. eGFR \<30 mL/min/1.73m² 4. Abnormal thyroid function (TSH \>6 mIU/L or \<0.4 mIU/L) 4. Pregnancy, planned pregnancy, or breastfeeding 5. 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 6. 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

Study locations

1 registered sites.

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

Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 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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