peg-rhgh and semaglutide combination therapy in non-diabetic obese adults

Conditions: Non-diabetic Obesity

Summary: this study aims to evaluate the efficacy and safety of peg-rhgh injection combined with semaglutide injection versus semaglutide injection monotherapy in improving body composition (lean body mass, fat mass, etc.) in non-diabetic obese adults, while also analyzing changes in body weight, blood glucose, and other metabolic parameters.


Eligibility criteria:
inclusion criteria: 1. age between 18 years (minimum age) and 50 years (maximum age), inclusive 2. gender: male or female, with a ratio of male to female being 2:1; 3. body mass index (bmi) ≥28 kg/m²; 4. no prior use of semaglutide injection or antidiabetic medications; 5. free thyroxine (ft4) levels within normal range at screening; 6. testosterone levels within normal range at screening (males only); 7. no plans for pregnancy from the time of signing the icf until 2 months after the study ends, willingness to take effective contraceptive measures to prevent pregnancy or causing a partner's pregnancy, and no plans for sperm or egg donation during the study period; 8. participants must voluntarily agree to and be able to comply with all scheduled visits, treatment plans, laboratory tests, special examinations, neurological assessments, and other trial procedures, and sign a written informed consent form. exclusion criteria: 1. unable to accept regular follow-up; 2. those who have difficulty with self-injection; 3. weight change \>5.0% in the 12 weeks prior to screening (self-reported); 4. history of allergic reactions to the study drug or similar drugs; 5. evaluated by the investigator as unable to tolerate subcutaneous injection, such as those undergoing anticoagulant therapy, thrombocytopenia, known bleeding disorders, or idiopathic thrombocytopenic purpura; 6. planning surgery within 1 year; history of gastrointestinal surgery (excluding polypectomy and appendectomy); 7. positive blood hcg during screening; breastfeeding women; postmenopausal women; women with fsh \>30 iu/l during screening; 8. any of the following: myocardial infarction, stroke, unstable angina requiring hospitalization, or transient ischemic attack within 180 days before screening, classified as nyha class iii or higher; 9. clinically significant severe ecg abnormalities (e.g., qt prolongation \[\>450 ms in men, \>470 ms in women\], ventricular flutter, ventricular fibrillation, torsades de pointes, sick sinus syndrome, third-degree heart block without pacemaker therapy, and other severe abnormalities as assessed by the investigator), uncontrolled blood pressure despite treatment/untreated (systolic bp ≥160 mmhg and/or diastolic bp ≥100 mmhg during screening, systolic bp \<90 mmhg and/or diastolic bp \<50 mmhg), or other cardiovascular diseases deemed unsuitable for the study by the investigator; 10. triglycerides ≥500 mg/dl (5.65 mmol/l); 11. current or past history of malignancy, or currently having nodules with malignant potential such as thyroid nodules with tirads grade ≥4; 12. tumor markers during screening: ca125 (for women), ca199, cea, afp above upper limit of normal range; psa above upper limit of normal range (for men); 13. hemoglobin a1c ≥6.5% during screening; 14. history of diabetes (type 1, type 2, special types, or gestational diabetes) or currently using injectable or oral antidiabetic medications; 15. current or past history of acromegaly; 16. proliferative or severe non-proliferative diabetic retinopathy at screening; fundus examination within 90 days before randomization: proliferative retinopathy or macular edema requiring acute treatment; 17. used growth hormone therapy in the past 6 months; 18. used any weight loss medications in the past 3 months; previously underwent obesity surgery or planned obesity surgery during the study; 19. any of the following laboratory tests at screening: ast or alt \>2.5 uln; total bilirubin \>1.5 uln; tsh \ 6 miu/l; calcitonin \>50 ng/l; 20. igf-1 sds \>2.0 (age and gender matched); 21. serum creatinine \>1.5 uln, egfr \<60 ml/min/1.73 m² \[using the modified simplified mdrd equation: egfr = 175 × (serum creatinine in mg/dl)\^-1.234 × age\^-0.179 × 0.79 for women\], or kidney impairment requiring dialysis; 22. history of pancreatitis, or current acute or chronic pancreatitis; 23. history of cholecystitis, or current gallbladder/biliary disease symptoms, or treatable gallstones or polyps; 24. family or personal history of multiple endocrine neoplasia type 2 or thyroid cancer (family defined as first-degree relatives); 25. prior history of pituitary mass; 26. history of seizures; 27. participated in another clinical trial with approved or investigational drugs/devices within 90 days before screening (excluding those who only signed the consent without receiving any intervention); 28. history of substance abuse and/or alcoholism, or mental disorders; during screening, had impaired consciousness including somnolence, stupor, coma, confusion; 29. questionnaire phq-9 score ≥15; history of suicidal behavior; columbia-suicide severity rating scale (c-ssrs) question 1 or 2 indicating suicidal ideation (answering "yes" to question 1 or 2); 30. other reasons for exclusion as deemed by the investigator, such as any situation endangering participant safety or affecting compliance with the protocol.