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

NCT07657676 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-3068
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Obesity & Overweight; Coronary Heart Disease

Keywords

GLP-1RA; CCTA; Mazdutide; Obesity; Plaque; Overweight; Coronary Heart Disease

Outcome Measures

Primary Outcomes (1)

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

  52 weeks

Secondary Outcomes (28)

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

  52 weeks

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

  52 weeks

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

  52 weeks

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

  52 weeks

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

  52 weeks

Study Arms (2)

Experimental: Mazdutide

EXPERIMENTAL

Drug: Mazdutide

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Mazdutide DRUG

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.

Experimental: Mazdutide

Placebo DRUG

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.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• Signed informed consent
• Willing to comply with follow-up

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• China National Center for Cardiovascular Diseases: lead

Study Sites (1)

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

Beijing, Beijing Municipality, 100037, China

Location

MeSH Terms

Conditions

Obesity; Overweight; Coronary Disease; Plaque, Amyloid

Interventions

mazdutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical

Study Officials

• Ke fei Dou

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

  PRINCIPAL INVESTIGATOR

• Xiao Wang

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao Wang

CONTACT

86-10-88396953; wangxiao@fuwai.com

Shuang Zhang

CONTACT

86-10-88396953; tats246@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: June 18, 2026
• Study Start: May 25, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)