An interventional study of Tirzepatide with lifestyle modification and Semaglutide with lifestyle modification in Obesity and Metabolic Syndrome, sponsored by Tri-Service General Hospital (TSGH). Recruiting at 1 site in Taiwan. Open to participants aged 20 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-05-15.
Sponsored by Tri-Service General Hospital (TSGH) · Not applicable, Interventional, and Treatment
This randomized, open label, head to head clinical trial directly compares tirzepatide and semaglutide in adults with obesity and metabolic syndrome (N=120, age 20-65, 1:1 randomization). Participants undergo deep phenotyping at baseline, 6 months, and 12 months, including DXA (regional fat, lean mass, and BMD), MRI PDFF (liver fat), 7 site skinfold thickness, grip strength, fasting biochemistry, and AI processed 12 lead ECGs. Centralized biobanking of serum, plasma, and PBMCs enables targeted and discovery multi omic analyses.
This study is a single-center, randomized, open-label, active-comparator trial designed to characterize the differential effects of tirzepatide and semaglutide on adipose tissue biology and cardiometabolic remodeling over 12 months in adults with obesity and metabolic syndrome. The trial integrates pharmacologic weight-loss therapy with multimodal phenotyping to quantify changes across body composition, hepatic steatosis, metabolic biomarkers, functional strength, and AI-derived electrophysiologic signatures.
The scientific premise is that incretin-based therapies may produce qualitatively distinct patterns of fat loss, ectopic fat mobilization, and cardiometabolic improvement. Tirzepatide, a dual GIP/GLP-1 receptor agonist, may induce greater reductions in visceral adiposity and hepatic fat compared with GLP-1 receptor agonism alone. This trial is designed to directly compare these mechanistic profiles using harmonized imaging, biochemical, and digital phenotyping platforms.
Participants are randomized 1:1 to tirzepatide or semaglutide using a computer-generated permuted block scheme stratified by sex and baseline BMI category. Both interventions follow standard titration schedules and are paired with structured lifestyle counseling to ensure comparable background care. Study visits occur at baseline, 3, 6, and 12 months, with deep phenotyping at baseline, 6, and 12 months.
The phenotyping framework emphasizes regional adiposity, lean mass preservation, hepatic steatosis, and cardiometabolic risk signatures. Whole-body DXA provides quantification of total and regional fat and lean mass, enabling derivation of fat-to-lean mass loss ratios and redistribution indices. Abdominal MRI with proton density fat fraction (PDFF) quantifies liver fat content and abdominal fat compartments. Functional and behavioral assessments-including grip strength and the Chinese version of the Weight-Related Eating Questionnaire-characterize changes in physical function and eating behavior patterns over time.
Fasting biochemical panels measure glycemic indices, lipid metabolism, inflammation, renal and hepatic function, and cardiometabolic biomarkers. Standard 12-lead ECGs are processed through a validated AI pipeline to generate electrophysiologic risk features (e.g., predicted ASCVD risk, ECG-derived heart age), which serve as exploratory digital biomarkers.
A centralized biobanking program supports mechanistic analyses. Serum, plasma, and PBMCs collected at each deep-phenotyping visit are stored under standardized SOPs for targeted and discovery-based metabolomic, proteomic, epigenetic and transcriptomic analyses. These biospecimens will enable downstream investigation of molecular pathways underlying differential treatment responses.
Together, this integrated platform allows for a comprehensive comparison of tirzepatide and semaglutide across structural, metabolic, functional, and molecular domains, providing mechanistic insight into how incretin-based therapies remodel adipose tissue and cardiometabolic physiology.
11,522 studies on the registry are indexed under Obesity; 2,033 are open to participants now.
This study's planned enrollment of 120 is above the median of 67 across 9,006 interventional studies indexed under Obesity.
Browse Obesity studies →Tri-Service General Hospital (TSGH) is the lead sponsor of 38 studies on the registry; 12 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
starting at 2.5 mg weekly and escalated every month (5.0 mg, 7.5 mg to 10 mg) as tolerated
Drug: Tirzepatide with lifestyle modification
starting at 0.25 mg weekly and escalated every month (0.5 mg, 1.0 mg, 1.7 mg to 2.4 mg) as tolerated
Drug: Semaglutide with lifestyle modification
Starting at Tirzepatide 2.5 mg weekly and escalated as tolerated to 10 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials.
Starting at Semaglutide 0.25 mg weekly and escalated as tolerated to 2.4 mg along with standardized lifestyle counseling by a dietitian (caloric deficit, physical activity guidance) and written materials.
This study also gives Semaglutide, Tirzepatide. No intervention listed here names it: that was found by reading the record.
Percent change in total body weight from baseline to 6 months.
Time frame: Baseline to 6 months
Total fat to lean mass loss ratio (DXA derived) from baseline to 6 months.
Time frame: Baseline to 6 months
Change in metabolic syndrome severity Z score from baseline to 6 months.
Time frame: Baseline to 6 months.
Change in waist circumference (cm)
Time frame: Baseline to 6 months and 12 months
Change in waist-to-hip ratio (unitless ratio)
Time frame: Baseline to 6 months and 12 months.
Change in regional fat mass measured by DXA (grams)
Time frame: Baseline to 6 months and 12 months.
Change in regional lean mass measured by DXA (grams)
Time frame: Baseline to 6 months and 12 months
Change in 7-site skinfold thickness (mm)
Time frame: Baseline to 6 months and 12 months.
Change in liver fat content measured by MRI-PDFF (percentage, %PDFF)
Time frame: Baseline to 6 months and 12 months
Change in abdominal visceral fat volume (mL)
Time frame: Baseline to 6 months and 12 months
Change in abdominal subcutaneous fat volume (mL)
Time frame: Baseline to 6 months and 12 months
Change in systolic and diastolic blood pressure (mmHg)
Time frame: Baseline to 6 months and 12 months
Change in fasting lipid profile (mg/dL)
Lipid profile includes total cholesterol, LDL-C, HDL-C and Triglycerides
Time frame: Baseline to 6 months and 12 months
Change in fasting glucose (mg/dL)
Time frame: Baseline to 6 and 12 months
Change in hsCRP (mg/L)
Time frame: Baseline to 6 and 12 months
Change in insulin sensitivity (HOMA-IR, unitless)
Time frame: Baseline to 6 and 12 months
Change in β-cell function (HOMA-β, percentage, %)
Time frame: Baseline to 6 and 12 months
Change in AI-ECG predicted ASCVD risk score (percentage, %)
Time frame: Baseline to 6 and 12 months
Change in ECG-derived heart age (years)
Time frame: Baseline to 6 and 12 months
Change in AI-ECG diabetes risk index (HbA1c, percentage, %)
Time frame: Baseline to 6 and 12 months
Change in estimated 10-year ASCVD risk (percentage, %)
Time frame: Baseline to 6 and 12 months
Change in bone mineral density (g/cm²)
Time frame: Baseline to 6 and 12 months
Change in serum P1NP (ng/mL)
Time frame: Baseline to 6 and 12 months
Change in serum CTX-1 (ng/mL)
Time frame: Baseline to 6 and 12 months
Change in fasting plasma metabolomics profile (relative abundance units)
Time frame: Baseline to 6 and 12 months
Change in fasting plasma proteomics profile (relative abundance units)
Time frame: Baseline to 6 and 12 months
Change in microRNA expression signatures (normalized expression units)
Time frame: Baseline to 6 and 12 months
Change in RNA-seq transcriptomic signatures (normalized counts, e.g., TPM)
Time frame: Baseline to 6 and 12 months
Change in epigenetic methylation signatures (Methylation, percentage, %)
Time frame: Baseline to 6 and 12 months
Change in depressive symptoms (scale score)
Instrument: e.g., PHQ-9
Time frame: Baseline to 6 and 12 months
Change in sleep quality (scale score)
Instrument: e.g., PSQI
Time frame: Baseline to 6 and 12 months
Change in quality of life (scale score)
Instrument: e.g., EQ-5D or SF-36
Time frame: Baseline to 6 and 12 months
Change in eating behavior (WREQ-C total and subscale scores)
Time frame: Baseline to 3, 6, and 12 months
Plan to share: No — It is still ongoing and can not be shared before the final analysis.
No publications or documents are linked to this record.
Started Mar 2026 (actual). Primary completion is estimated for Sep 2028, 29 months after the start.
Of 3,680 non-industry interventional studies with no phase under Obesity, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 43. This study's planned 29 months is above that.
Counting every sponsor, half of 3,843 studies reached it within 22 months; a quarter within 10 and three quarters within 42.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drugs tested here: Semaglutide · Tirzepatide
Tri-Service General Hospital (TSGH)