Efficacy of Mazdutide on Fatty Pancreas in Overweight or Obese Adults: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 194
- 试验地点
- 1
- 主要终点
- Percentage change in Intrapancreatic Fat Deposition (IPFD) from baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients participating in this study must meet all of the following criteria:
- •Age 18-60 years (inclusive) at screening, regardless of gender;
- •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.);
- •Pancreatic MRI-PDFF quantitative assessment completed during the screening period, with intrapancreatic fat deposition (IPFD) ≥6%;
- •Fully informed about the study and voluntarily signed written informed consent;
- •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]:
- •Abdominal obesity (central obesity): Waist circumference ≥90 cm in men, ≥85 cm in women;
- •Fasting blood glucose ≥6.1 mmol/L and/or 2-hour postprandial blood glucose ≥7.8 mmol/L, and/or diagnosed diabetes under treatment;
- •Blood pressure ≥130/85 mmHg, and/or diagnosed hypertension under treatment;
- •Fasting triglycerides (TG) ≥1.7 mmol/L;
- •Fasting HDL-C <1.04 mmol/L.
排除标准
- •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.
研究组 & 干预措施
Control group
standardized lifestyle intervention + placebo
干预措施: Placebo matching mazdutide (Other)
Intervention group
standardized lifestyle intervention + mazdutide
干预措施: mazdutide (Drug)
结局指标
主要结局
Percentage change in Intrapancreatic Fat Deposition (IPFD) from baseline
时间窗: 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%.
次要结局
- Change in visceral fat area(From baseline to Week 48)
- Change in Body Mass Index (BMI)(From baseline to Week 48)
- Change in body weight(From baseline to Week 48)
- Change in waist circumference(From baseline to Week 48)
- Change in basal metabolic rate (BMR)(From baseline to Week 48)
- Changes in complete blood count (CBC) parameters(From baseline to Week 48)
- Changes in liver function tests(From baseline to Week 48)
- Changes in renal function tests(From baseline to Week 48)
- Changes in lipid profile(From baseline to Week 48)
- Changes in pancreatic enzymes (amylase/lipase)(From baseline to Week 48)
- Change in glycated hemoglobin (HbA1c)(From baseline to Week 48)
- Changes in glucose metabolism indices (OGTT + IRT)(From baseline to Week 48)
- Changes in inflammatory markers (IL-6, TNF-α)(From baseline to Week 48)
研究者
Yan Yang, MD, PhD
Principal Investigator
Tongji Hospital