Obesity & Overweight
Conditions
Keywords
Semaglutide, Weight loss maintenance, Dose-tapering, Obesity
Brief summary
The goal of this clinical trial is to determine whether a semaglutide dose-tapering regimen is non-inferior to a treatment-dose maintenance regimen for weight-loss maintenance in adults with overweight or obesity who have achieved stable weight loss. This trial will also evaluate the safety of the dose-tapering regimen. The primary research questions are: Is the semaglutide dose-tapering regimen non-inferior to the treatment-dose maintenance regimen for weight-loss maintenance at 24 weeks? Can the dose-tapering regimen alleviate adverse events and offer a more personalized, sustainable pathway for medication discontinuation? Researchers will compare the semaglutide dose-tapering regimen against a treatment-dose maintenance regimen to assess whether the tapering strategy preserves weight loss and improves cardiometabolic markers. Participants will: Be randomly assigned to receive either the semaglutide dose-tapering regimen or the treatment-dose maintenance regimen for 24 weeks. Complete a 24-week follow-up period after medication discontinuation (48 weeks total study duration). Attend scheduled clinic visits for physical examinations and laboratory testing to assess weight, BMI, waist circumference, cardiometabolic markers (including blood glucose, blood pressure, and lipids), and to monitor adverse events.
Interventions
DRUGSemaglutide Dose-Tapering Regimen
Semaglutide dose-tapering regimen: Subjects initiate from a stable entry dose of 1.7 mg per week, with a 25% relative dose reduction implemented every 8 weeks over the 24-week intervention period.
DRUGSemaglutide Maintenance-Dose Regimen
Subjects keep the stable entry dose of 1.7 mg once-weekly without any dose modification during the full 24-week intervention period.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, aged 18 to 64 years inclusive at the time of signing the informed consent form. * Ongoing weight-loss treatment consisting of weekly semaglutide, with a documented weight reduction of ≥ 10% of pre-treatment body weight, or a weight reduction between 5% and \< 10% concurrent with a BMI \< 25 kg/m². * Maintained on a weekly semaglutide dose of 1.7 mg, with a stable weight over the 12 weeks prior to enrollment (less than 5% change in body weight). * Voluntarily participating in the study, capable of effective communication with the investigators, willing to comply with all study procedures, and having provided written informed consent.
Exclusion criteria
* History or planned bariatric surgery or use of a weight-loss device during the trial. * Obesity induced by other endocrinologic disorders or monogenic mutations, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroidism, Cushing's syndrome, insulinoma, acromegaly, or hypogonadism. * Glycated hemoglobin (HbA1c) ≥ 6.5% as measured by a local laboratory at screening, or a history of diabetes mellitus (excluding a history of gestational diabetes). * Use of any weight-loss medications (e.g., tirzepatide, mazdutide, liraglutide, orlistat, sibutramine, phenylpropanolamine, chlorpheniramine, phentermine, lorcaserin, phendimetrazine, phentermine-topiramate, or naltrexone-bupropion), herbal medicines, dietary supplements, or meal replacements affecting body weight within 90 days prior to screening (except semaglutide and lifestyle interventions). Use of medications that may cause significant weight gain, including systemic glucocorticoids for more than 1 week, antipsychotics or antiepileptics (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, clozapine, olanzapine, valproic acid and its derivatives, lithium preparations, thioridazine), or growth hormone. * History of acute or chronic pancreatitis, or presence of high-risk factors such as a history of pancreatic injury. Current or past history of malignancies (except for localized basal cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the prostate). Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2, including MEN 2A and MEN 2B). * End-stage renal disease, or requiring long-term/intermittent hemodialysis or peritoneal dialysis. * Occurrence of any of the following within 60 days prior to screening: myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack (TIA). * Current New York Heart Association (NYHA) class IV heart failure. * Known or suspected hypersensitivity to the investigational product or related products. * Participation in another clinical trial within 90 days prior to screening. * Female patients who are pregnant, breastfeeding, or planning to become pregnant within the next two years. * History of major depressive disorder or a diagnosis of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder) within 2 years prior to screening. * History of attempted suicide. * Abnormal laboratory results at screening: severe hepatic or renal impairment, such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × upper limit of normal (ULN); bilirubin \> 2.5 × ULN (except for known Gilbert's syndrome meeting the criteria of fractionated conjugated bilirubin \< 35% of total bilirubin); triglycerides ≥ 5.7 mmol/L. * Unstable proliferative retinopathy or maculopathy requiring urgent treatment within 1 year prior to screening, or a history of diabetic ketoacidosis, diabetic hyperosmolar nonketotic coma, or severe metabolic disorders leading to neurological or psychiatric dysfunction. * History or risk factors of the following: clinically significant anemia, epilepsy, syncope, cardiac arrest, arrhythmia, atrioventricular block, structural heart disease, or torsades de pointes. * Severe active bacterial, viral, or fungal infections requiring hospitalization or intravenous antibiotic therapy. * History of infectious diseases, including but not limited to HIV/AIDS, syphilis, or active infectious hepatitis. * History of alcohol dependence or substance abuse within 6 months prior to screening. * Any other condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in body weight from baseline to week 24 | Baseline (Week 0) to Week 24 | Body weight is measured with a calibrated medical electronic scale (accurate to 0.1 kg). Subjects are weighed in the morning after an overnight fast, post-voiding, barefoot, and wearing light clothing. Percentage change is calculated as \[(Week 24 body weight - baseline body weight) / baseline body weight\] × 100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in body weight from baseline to week 24 (kg) | Baseline (Week 0) to Week 24 | Measured using a calibrated medical electronic scale (accurate to 0.1 kg). Subjects will be weighed in the morning after an overnight fast, post-voiding, barefoot, and wearing light clothing. The absolute difference between baseline and week 24 body weight will be calculated. |
| Mean change in waist circumference from baseline to week 24 (cm) | Baseline (Week 0) to Week 24 | Measured using a non-stretchable standard measuring tape (accurate to 0.1 cm). Waist circumference will be measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest in the mid-axillary line at the end of a normal expiration. The change from baseline is calculated. |
| Mean change in body mass index (BMI) from baseline to week 24 (kg/m²) | Baseline (Week 0) to Week 24 | Height is measured using a standard stadiometer (accurate to 0.1 cm). Combined with the weight measured at the same timepoint, BMI is calculated using the formula: weight (kg) / height (m)². |
Contacts
CONTACTYunfei Liao, PhD
Outcome results
None listed