A Phase 4 interventional study of Tirzepatide and Semaglutide in Obesity (Disorder), sponsored by McMaster University. Recruiting at 1 site in Canada. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-10-28.
Sponsored by McMaster University · Phase 4, Interventional, and Treatment
The goal of this clinical trial is to determine if there are differences in the effect of 12 weeks of tirzepatide versus semaglutide on energy balance in adults with obesity and without known diabetes. The main questions it aims to answer are:
- Does tirzepatide have a greater effect on energy expenditure or energy extraction than semaglutide?
Participants will:
The Joule 3 Drug Trial study is a single-centre, randomized controlled trial designed to investigate the effects of 12 weeks of tirzepatide versus semaglutide on energy balance: energy expenditure (EE) and its components, energy intake, and energy extraction from food. We will also determine if there is an impact on the activity of thermogenic brown adipose tissue, self-reported appetite and satiety, gut microbiota composition, and body composition.
This study will be conducted in adults (aged 18-60) with obesity and without known diabetes.
Tirzepatide and semaglutide will be self-injected subcutaneously once weekly, increasing by one dose level every 4 weeks, if tolerated by the participant. Participants will attend baseline and week 12 study visits. Each of these visits will be preceded by a 3-day meal plan and stool collection. During these visits, participants will enter an indirect whole room calorimeter for \~23 hours to measure energy expenditure and its components (resting EE, sleep EE, diet induced EE, activity induced EE) and energy intake. Participants will also undergo an MRI at these visits to assess brown adipose tissue activity and anthropometrics and body composition will be measured.
11,522 studies on the registry are indexed under Obesity; 2,033 are open to participants now.
This study's planned enrollment of 80 is above the median of 67 across 9,006 interventional studies indexed under Obesity.
Browse Obesity studies →McMaster University is the lead sponsor of 741 studies on the registry; 127 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
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.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
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.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This group will take semaglutide once weekly for 12 weeks. Participants will be started at 0.25 mg and increase by one dose level every 4 weeks, if tolerated (allowing up to 3 dose levels over 12 weeks), to a maximum dose of 1 mg. Dose levels are 0.25 mg, 0.5 mg, 1 mg.
Drug: Semaglutide
This group will take tirzepatide once weekly for 12 weeks. Participants will be started at 2.5 mg and increase by one dose level every 4 weeks, if tolerated (allowing up to 3 dose levels over 12 weeks), to a maximum dose of 7.5 mg. Dose levels are 2.5 mg, 5 mg, 7.5 mg.
Drug: Tirzepatide
This group will take tirzepatide once weekly for 12 weeks. Participants will be started at 2.5 mg and increase by one dose level every 4 weeks, if tolerated (allowing up to 3 dose levels over 12 weeks), to a maximum dose of 7.5 mg. Dose levels are 2.5 mg, 5 mg, 7.5 mg.
This group will take semaglutide once weekly for 12 weeks. Participants will be started at 0.25 mg and increase by one dose level every 4 weeks, if tolerated (allowing up to 3 dose levels over 12 weeks), to a maximum dose of 1 mg. Dose levels are 0.25 mg, 0.5 mg, 1 mg.
24-hour Energy Expenditure Measured Using Whole Room Indirect Calorimetry
24-hour energy expenditure will be measured using whole room indirect calorimeter. Metabolic rate in kcal/day will be estimated using the Weir formula, from inspired oxygen and expired carbon dioxide measured every minute by software in the Promethium System, summed over 23 hours and extrapolated to 24 hours by multiplying by 24/23.
Time frame: Baseline, 12 Weeks
Components of 24-hour Energy Expenditure (EE)
Resting EE (REE), sleep EE (SEE), diet induced EE (DEE), and activity induced EE (AEE) will be measured using the whole room indirect calorimeter. REE is the intercept of the regression line of EE on activity counts per minute (cpm) determined by accelerometry (i.e., EE at 0 cpm). SEE is defined as the lowest average EE over 3 hours of sleep from 0000h to 0700h and multiplied by 8 to be expressed as kcal/day. DEE is calculated a) as the difference between REE and SEE (this value also includes the energy expended to be awake) and b) as the additional energy expended over 4 hours after breakfast above EE measured at rest first thing in the morning. AEE will be calculated a) as the difference between 24h EE and REE, and b) as the energy expended during a standardized exercise bout in the afternoon. Participants will maintain a cadence of approximately 60 rpm for three 6-minute segments at increasing power.
Time frame: Baseline, 12 Weeks
Energy Intake
Energy intake under controlled ad libitum conditions will be assessed by measuring the caloric content of an ad libitum lunch and dinner meals of standardized macronutrient composition provided in the whole room indirect calorimeter.
Time frame: Baseline, 12 Weeks
Energy Extraction from Food
To calculate the energy extraction from food passing through the gastrointestinal tract, pills containing nonabsorbable dyes will be ingested at the beginning and end of the 3-day free-living meal plan. Participants will collect all feces from appearance of the first dye until appearance of the second dye. Energy in homogenized feces will be accurately measured in the bomb calorimeter using established procedures. Energy extraction will be calculated as difference between energy intake (based on food provided and returned) and calories in the feces, and will be expressed as kcal/day and a percentage of energy intake.
Time frame: Baseline, 12 Weeks
Brown Adipose Tissue (BAT) Activity
To evaluate cold-stimulated BAT activity, MRI scans to quantify proton density fat fraction (PDFF) and T2\* in the supraclavicular region of the neck between the levels of C2/C3 disc and the T4/T5 disc will be performed before and after cold exposure using a full-body water-perfused suit, at 18°C for 1 hour.
Time frame: Baseline, 12 Weeks
Appetite and Satiety
Appetite and satiety will be assessed using validated visual scales scored 0-100 before breakfast, 30 minutes later and hourly for 4 hours while in the whole room indirect calorimeter.
Time frame: Baseline, 12 Weeks
Stool Microbiota Composition
Stool microbiota analysis completed using 16S rRNA primers will include α-diversity (amplicon sequence variants (ASVs) richness and evenness within each sample) and β-diversity (between samples), and predicted functional metagenomics using PICRUSt or similar software.
Time frame: Baseline, 12 Weeks
Body Composition
Body composition will be measured using a dual-energy X-ray absorptiometry (DXA) scan and bioelectrical impedance analysis (BIA).
Time frame: Baseline, 12 Weeks
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Tirzepatide · Semaglutide