Efficacy of Mazdutide on Fatty Pancreas

September 17, 2026 updated by: Yan Yang, MD, PhD, Tongji Hospital

Efficacy of Mazdutide on Fatty Pancreas in Overweight or Obese Adults: A Randomized Controlled Trial

This is a randomized, double-blind, placebo-controlled, parallel-group, single-center clinical trial designed to evaluate the efficacy and safety of mazdutide in improving fatty pancreas in patients with overweight or obesity. The study plans to enroll 194 participants with overweight or obesity, who will be randomly assigned in a 1:1 ratio to either the mazdutide plus standardized lifestyle intervention group or the placebo plus standardized lifestyle intervention group, for a treatment duration of 48 weeks. The primary efficacy endpoint is the change from baseline in pancreatic proton density fat fraction (PDFF) measured by MRI at week 48. Secondary efficacy endpoints include changes in body weight, body mass index (BMI), waist circumference, glycemic and lipid metabolic parameters, visceral fat, and hepatic fat content. This study aims to provide preliminary evidence-based data supporting the application of mazdutide in the treatment of fatty pancreas associated with metabolic dysfunction.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Fatty pancreas is a clinicopathological syndrome characterized by fat infiltration in pancreatic tissue. It can be classified into three categories based on etiology and risk factors: ectopic pancreatic fat deposition due to overnutrition and metabolic dysfunction, secondary fatty replacement following pancreatic injury from various causes, and fatty pancreas associated with genetic or congenital diseases. Among these, excessive fat deposition within pancreatic tissue occurring against the backdrop of metabolic abnormalities is termed metabolic dysfunction-associated fatty pancreas (MAFP), which is commonly seen in individuals with overweight, obesity, or metabolic syndrome. MAFP can impair both endocrine and exocrine pancreatic functions, increase the risks of pancreatitis and glucose metabolism disorders, and significantly elevate the incidence of pancreatic cancer. Currently, there are no approved specific pharmacotherapies for fatty pancreas. Although lifestyle intervention serves as the foundational treatment, long-term patient adherence remains limited. Existing studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can effectively reduce visceral and ectopic fat deposition, lowering absolute pancreatic fat content by approximately 2%-6%, thereby demonstrating potential as therapeutic agents for MAFP. Mazdutide, a dual GLP-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist, synergistically activates dual metabolic pathways, reducing visceral fat accumulation while achieving potent weight loss. Based on its unique mechanism of action and established evidence for weight reduction, mazdutide holds promising application prospects for alleviating MAFP and managing metabolic comorbidities. However, no dedicated studies have yet evaluated the impact of mazdutide on pancreatic fat content in obese patients.

Study Type

Interventional

Enrollment (Estimated)

194

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430030
        • TongjHospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Patients participating in this study must meet all of the following criteria:

  1. Age 18-60 years (inclusive) at screening, regardless of gender;
  2. BMI at screening meets one of the following conditions: ① BMI ≥28 kg/m²; or ② 24 kg/m² ≤ BMI <28 kg/m², with at least one obesity-related metabolic abnormality (elevated fasting blood glucose, dyslipidemia, hypertension, etc.);
  3. Pancreatic MRI-PDFF quantitative assessment completed during the screening period, with intrapancreatic fat deposition (IPFD) ≥6%;
  4. Fully informed about the study and voluntarily signed written informed consent;
  5. Agreed to maintain a stable lifestyle (including diet and exercise habits) during the study.

Note: Diagnostic criteria for Metabolic Syndrome (meeting ≥3 of the following items) [ChineseDiabetesSociety(CDS)2020]:

  1. Abdominal obesity (central obesity): Waist circumference ≥90 cm in men, ≥85 cm in women;
  2. Fasting blood glucose ≥6.1 mmol/L and/or 2-hour postprandial blood glucose ≥7.8 mmol/L, and/or diagnosed diabetes under treatment;
  3. Blood pressure ≥130/85 mmHg, and/or diagnosed hypertension under treatment;
  4. Fasting triglycerides (TG) ≥1.7 mmol/L;
  5. Fasting HDL-C <1.04 mmol/L.

Exclusion Criteria:

Participants meeting any of the following conditions will be excluded from this study:

Glycated hemoglobin HbA1c ≥7.5% at screening; history of diabetic ketoacidosis (DKA) or other diabetic emergencies; Use within 3 months before screening of glucagon-like peptide-1 receptor (GLP-1R) agonists, GLP-1R/glucagon receptor (GCGR) dual agonists, glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP-1R agonists, GIPR/GLP-1R/GCGR triple agonists, insulin, or oral antidiabetic drugs other than metformin; Use of any weight-loss drug or fat-reducing dietary supplement within 1 month before screening/enrollment; or use within 1 month before screening of systemic medications that may cause weight gain, including systemic glucocorticoids, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers; Self-reported or documented weight fluctuation of >5% within 3 months before screening; Current or history of acute pancreatitis or chronic pancreatitis; or serum triglycerides (TG) >5.6 mmol/L at screening; or history of acute cholecystitis or symptomatic/requiring-treatment gallbladder disease (except participants who have undergone cholecystectomy and are judged by the investigator to be eligible); Chronic kidney disease stage 3 or higher, eGFR <60 mL/min/1.73 m² (calculated by CKD-EPI formula); Obesity secondary to other endocrine diseases, such as Cushing syndrome; Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (MTC); History of malignancy within 5 years before screening (except cured basal cell carcinoma of the skin, cervical carcinoma in situ, etc.); Acute myocardial infarction, unstable angina, coronary revascularization, stroke, or transient ischemic attack within 6 months before screening; or New York Heart Association (NYHA) class III or IV heart failure; Acute or chronic hepatitis at screening (except chronic hepatitis B), autoimmune hepatitis, or significantly abnormal liver function: ALT or AST >3×ULN, or total bilirubin >2×ULN (except Gilbert syndrome); History of pancreatic injury; imaging findings suggestive of pancreatic space-occupying lesion, pancreatic atrophy, pancreatic calcification, or history of pancreatic surgery that may affect IPFD assessment; Contraindications to MRI examination (e.g., metallic implants in the body, claustrophobia, etc.) or inability to cooperate with breath-holding for the examination; Blood amylase or lipase >2×ULN at screening; Pregnant or lactating women, or positive pregnancy test at screening; women of childbearing potential who are unwilling to use medically accepted contraception during the study; Allergy to GLP-1 receptor agonists or any component of the study drug; or prior discontinuation of GLP-1 receptor agonist drugs due to safety or tolerability reasons; Participation in another interventional clinical trial within 3 months before screening; History of major depressive disorder, or current severe psychiatric illness (e.g., schizophrenia, bipolar disorder, etc.) judged by the investigator to be unable to comply with study procedures; History of conditions affecting gastric emptying (e.g., gastric bypass surgery, pyloric stenosis, severe diabetic gastroparesis, etc.), long-term use of drugs directly affecting gastrointestinal motility, severe gastrointestinal diseases (e.g., active peptic ulcer, inflammatory bowel disease, etc.), or prior gastrointestinal surgery (except surgeries with no significant effect on gastrointestinal motility, such as gastrointestinal polypectomy, appendectomy, and hemorrhoid surgery); Severe infection, severe trauma, or major or moderate surgery within 1 month before screening; Severe ECG abnormalities at screening (e.g., QTcF >450 ms, supraventricular tachycardia, atrial fibrillation, atrial flutter, second- or third-degree atrioventricular block, etc.), or poorly controlled blood pressure: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg; Additional laboratory criteria: alkaline phosphatase (ALP) ≥2×ULN; calcitonin ≥50 ng/L; thyroid-stimulating hormone (TSH) <0.4 or >6.0 mIU/L; hemoglobin <100 g/L; Presence of acute or chronic hepatitis, or history of other severe liver diseases except metabolic-associated fatty liver disease; presence of significant hematologic diseases (e.g., sickle cell disease, hemolytic anemia, myelodysplastic syndrome, etc.) or diseases causing hemolysis/red blood cell instability; presence of autoimmune disease with planned systemic glucocorticoid or immunosuppressant therapy during the study; prior organ or bone marrow transplantation or planned transplantation during the trial; Known or suspected history of excessive alcohol consumption (weekly ethanol intake ≥210 g for men and ≥140 g for women for >3 months), or history of drug abuse or illicit drug use; Any other condition that, in the investigator's opinion, may affect compliance or safety assessment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group
standardized lifestyle intervention + mazdutide
Drug: mazdutide
On the basis of standardized lifestyle intervention, patients received mazdutide injection (prefilled auto-injector pen) via weekly subcutaneous injection (abdominal), following a dose-escalation regimen: an initial dose of 2 mg for weeks 1-4, escalation to 4 mg for weeks 5-8, and a maintenance dose of either 4 mg or 6 mg starting from week 9 (determined by tolerability and efficacy), with a treatment duration of 48 weeks.
Other Names:
  • IBI-362; LY3305677
Placebo Comparator: Control group
standardized lifestyle intervention + placebo
Other: Placebo matching mazdutide
On the basis of standardized lifestyle intervention, patients received a placebo injection identical to mazdutide injection in appearance, volume, and administration route, via weekly subcutaneous injection (abdominal), with a treatment duration of 48 weeks.
Other Names:
  • Placebo matching IBI-362

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage change in Intrapancreatic Fat Deposition (IPFD) from baseline
Time Frame: From baseline to Week 48
The relative percentage change in IPFD measured by pancreatic MRI-PDFF at Week 48 compared to baseline, calculated as: [(IPFDatWeek48-BaselineIPFD)/BaselineIPFD] × 100%.
From baseline to Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in visceral fat area
Time Frame: From baseline to Week 48
Absolute change in visceral fat area (measured by MRI or CT, as per protocol specification) from baseline.
From baseline to Week 48
Change in Body Mass Index (BMI)
Time Frame: From baseline to Week 48
Absolute change in BMI (kg/m²) from baseline.
From baseline to Week 48
Change in body weight
Time Frame: From baseline to Week 48
Absolute change in body weight (kg) from baseline.
From baseline to Week 48
Change in waist circumference
Time Frame: From baseline to Week 48
Absolute change in waist circumference (cm) from baseline.
From baseline to Week 48
Change in basal metabolic rate (BMR)
Time Frame: From baseline to Week 48
Absolute change in BMR (kcal/day) from baseline.
From baseline to Week 48
Changes in complete blood count (CBC) parameters
Time Frame: From baseline to Week 48
Evaluation of changes in hematology parameters (e.g., WBC, RBC, Hb, PLT) compared to baseline.
From baseline to Week 48
Changes in liver function tests
Time Frame: From baseline to Week 48
Evaluation of changes in ALT, AST, ALP, GGT, total bilirubin, etc., compared to baseline.
From baseline to Week 48
Changes in renal function tests
Time Frame: From baseline to Week 48
Evaluation of changes in serum creatinine, BUN, eGFR, etc., compared to baseline.
From baseline to Week 48
Changes in lipid profile
Time Frame: From baseline to Week 48
Evaluation of changes in total cholesterol, triglycerides, HDL-C, LDL-C, etc., compared to baseline.
From baseline to Week 48
Changes in pancreatic enzymes (amylase/lipase)
Time Frame: From baseline to Week 48
Evaluation of changes in serum amylase and lipase levels compared to baseline.
From baseline to Week 48
Change in glycated hemoglobin (HbA1c)
Time Frame: From baseline to Week 48
Absolute change in HbA1c (%) from baseline
From baseline to Week 48
Changes in glucose metabolism indices (OGTT + IRT)
Time Frame: From baseline to Week 48
Changes in fasting plasma glucose, 2-hour postprandial glucose, and insulin resistance index (HOMA-IR or similar) derived from OGTT and insulin release test, compared to baseline.
From baseline to Week 48
Changes in inflammatory markers (IL-6, TNF-α)
Time Frame: From baseline to Week 48
Absolute change in serum levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) from baseline.
From baseline to Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tongji Hospital

Investigators

  • Principal Investigator: Yan Yang, Tongji Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 15, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

August 31, 2026

First Submitted That Met QC Criteria

September 2, 2026

First Posted (Actual)

September 4, 2026

Study Record Updates

Last Update Posted (Actual)

September 18, 2026

Last Update Submitted That Met QC Criteria

September 17, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • nfm-GLP-1 RA -202601

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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