Efficacy of Mazdutide on Fatty Pancreas

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: Obesity; Overweight; Fatty Pancreas
• Intervention / Treatment: Drug: mazdutide; Other: Placebo matching mazdutide

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

• Study Contact: Name: Delin Ma; Phone Number: 86-027 83665513; Email: maderine4@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • TongjHospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Yan Yang; Phone Number: 86-027-83665513; Email: yy2025ywsy@163.com

Participation Criteria

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:

Patients with any of the following conditions will be excluded from participation in this study:

1. HbA1c ≥6.5% at screening; history of diabetic ketoacidosis (DKA) or other diabetic emergencies;
2. Use of GLP-1 receptor agonists (GLP-1RA), DPP-4 inhibitors, or insulin within 3 months prior to screening;
3. Use of any weight-loss drugs or dietary supplements for fat reduction within 1 month prior to screening enrollment; or use of systemic medications known to cause weight gain within 1 month prior to screening, including systemic glucocorticoids, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers;
4. Self-reported or documented significant weight fluctuation (>5%) within 3 months prior to screening;
5. Current or history of acute pancreatitis, chronic pancreatitis, or gallbladder disease (gallstones, cholecystitis); or serum triglycerides (TG) >5 mmol/L during the screening period;
6. Chronic kidney disease stage 3 or higher, eGFR <60 mL/(min·1.73m²) (calculated using the CKD-EPI formula);
7. Obesity secondary to other endocrine disorders, such as Cushing's syndrome;
8. Personal or family history of Multiple Endocrine Neoplasia type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC);
9. History of severe depression, or current severe psychiatric illness (schizophrenia, bipolar disorder, etc.), where the investigator judges that the patient cannot comply with the study procedures;
10. History of allergy to Tirzepatide injection or its excipients;
11. Pregnant or lactating women; women of childbearing potential unwilling to adopt effective contraceptive measures throughout the study and for 3 months after the last dose;
12. Contraindications to MRI examination (e.g., magnetic metal implants in the body, severe claustrophobia), preventing completion of pancreatic MRI-PDFF assessment;
13. Participation in other drug or medical device clinical trials within 3 months prior to screening;
14. Other serious organic diseases judged by the investigator to interfere with efficacy/safety evaluation or pose a risk to subject safety.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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	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	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)	Absolute change in BMI (kg/m²) from baseline.	From baseline to Week 48
Change in body weight	Absolute change in body weight (kg) from baseline.	From baseline to Week 48
Change in waist circumference	Absolute change in waist circumference (cm) from baseline.	From baseline to Week 48
Change in basal metabolic rate (BMR)	Absolute change in BMR (kcal/day) from baseline.	From baseline to Week 48
Changes in complete blood count (CBC) parameters	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	Evaluation of changes in ALT, AST, ALP, GGT, total bilirubin, etc., compared to baseline.	From baseline to Week 48
Changes in renal function tests	Evaluation of changes in serum creatinine, BUN, eGFR, etc., compared to baseline.	From baseline to Week 48
Changes in lipid profile	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)	Evaluation of changes in serum amylase and lipase levels compared to baseline.	From baseline to Week 48
Change in glycated hemoglobin (HbA1c)	Absolute change in HbA1c (%) from baseline	From baseline to Week 48
Changes in glucose metabolism indices (OGTT + IRT)	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)	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

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Yan Yang, Tongji Hospital

Study record dates

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 4, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: overweight or obesity; Mazdutide; Fatty Pancreas
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; mazdutide
• 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