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
- •Patients with any of the following conditions will be excluded from participation in this study:
- •HbA1c ≥6.5% at screening; history of diabetic ketoacidosis (DKA) or other diabetic emergencies;
- •Use of GLP-1 receptor agonists (GLP-1RA), DPP-4 inhibitors, or insulin within 3 months prior to screening;
- •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;
- •Self-reported or documented significant weight fluctuation (>5%) within 3 months prior to screening;
- •Current or history of acute pancreatitis, chronic pancreatitis, or gallbladder disease (gallstones, cholecystitis); or serum triglycerides (TG) >5 mmol/L during the screening period;
- •Chronic kidney disease stage 3 or higher, eGFR <60 mL/(min·1.73m²) (calculated using the CKD-EPI formula);
- •Obesity secondary to other endocrine disorders, such as Cushing's syndrome;
- •Personal or family history of Multiple Endocrine Neoplasia type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC);
- •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;
- •History of allergy to Tirzepatide injection or its excipients;
- •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;
- •Contraindications to MRI examination (e.g., magnetic metal implants in the body, severe claustrophobia), preventing completion of pancreatic MRI-PDFF assessment;
- •Participation in other drug or medical device clinical trials within 3 months prior to screening;
- •Other serious organic diseases judged by the investigator to interfere with efficacy/safety evaluation or pose a risk to subject safety.
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