Efficacy of Mazdutide on Fatty Pancreas

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.