Obesity (Disorder)Phase 4JOULE3NCT07900074
Mechanisms of Weight Loss: Tirzepatide vs Semaglutide
A Phase 4 study testing Tirzepatide and Semaglutide in people with Obesity (Disorder), run by McMaster University at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Obesity (Disorder)
- What is being tested?
- Tirzepatide and Semaglutide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteCanada
- Study dates
- 31 Oct 2026to 31 Dec 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-60 years
- Body mass index (BMI) >30 kg/m2
- Stable body weight (<5kg change in the 3 months prior to screening)
Who cannot join
- History of type 1 or type 2 diabetes or current diagnosis
- Glucose-lowering or weight loss drugs in the last 3 months or planned in the next 3 months
- Prior or planned bariatric surgery or planned low calorie meal program in the next 3 months
- Known clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction) or chronic GI symptoms (nausea, vomiting, diarrhea, constipation, bloating or unexplained abdominal pain) or chronically take drugs that directly affect GI motility
- Known liver disease other than non-alcoholic fatty liver disease, or ALT >3x ULN
- Intake of standard alcoholic drinks more than 21/week for men, or 14/week for women
Show all 20Show fewer
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2
- History of pancreatitis
- Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2
- Currently pregnant/breastfeeding, previous pregnancy within the last 6 months, or unwillingness to use contraception for 3 months
- Other medications, allergies or comorbidities that, in the opinion of the investigator could interfere with study medication or study measures (e.g., catecholamine medications) or current medication use that has been unstable in the past 8 weeks or expected to change within the next 3 months
- Claustrophobia precluding a 24 hour stay in a whole room calorimeter or MRI scan
- Inability to undergo MRI (weight >250 kg, incompatible implanted device, e.g., pacemaker)
- Use of cannabis or its related products (d-9-THC, CBD, d-8-THC, and cannabinol) in the past three months
- Use of nicotine/tobacco that has been unstable in the past 8 weeks or expected to change within the next 3 months (exclusion from MRI visit ONLY)
- Known monogenic, syndromic hypothalamic causes of obesity
- Not able to communicate in English
- History of cardiac conditions that precludes exercise
- Participation in any intervention clinical study within 90 days before screening
- History of eating disorder within the last year
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
McMaster University
Hamilton, Ontario, L8S 4L8
Autumn Lawrence, MSc, 289-251-2187, lawrea8@mcmaster.ca
Aaron Thomas, PhD, 605-525-9140 ext. 28083, thomasac@mcmaster.ca
About this study
Official title: Mechanisms of Weight Loss Due to Dual GIP GLP-1 Receptor Agonism With Tirzepatide Compared to Semaglutide: A Randomized Controlled Trial
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:
- Take tirzepatide or semaglutide once weekly for 12 weeks
- Undergo identical baseline and week 12 study visits (including 24-hour whole room indirect calorimeter testing, MRI scan, body composition, 3-day meal plan and stool collection)
Read the detailed description
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.
- Conditions
- Obesity (Disorder)
- Being tested
- Tirzepatide, Semaglutide
- Keywords
- Obesity, Semaglutide, Tirzepatide, Energy balance, Energy expenditure, GLP-1 receptor agonist, dual GIP GLP-1 receptor agonist, Weight loss, Weight loss drug, Whole room indirect calorimetry, MRI, Brown adipose tissue, Cold exposure
- Medical subject headings
- Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
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.
SemaglutideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | 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. Receives: Drug: Semaglutide |
| Tirzepatide | Experimental | 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. Receives: Drug: Tirzepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 12 Weeks
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 12 Weeks
Body Composition
Body composition will be measured using a dual-energy X-ray absorptiometry (DXA) scan and bioelectrical impedance analysis (BIA).
Measured: Baseline, 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study start31 Oct 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity (Disorder)Studies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zubin Punthakee, McMaster University
- Investigators
- Zubin Punthakee, MD, MSc, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07900074
- Sponsor's protocol ID
- 19795
- Acronym
- JOULE3
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Weight Loss Due to Dual GIP GLP-1 Receptor Agonism With Tirzepatide Compared to Semaglutide: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07900074
- Acronym / sponsor ID
- JOULE3 / 19795
- Conditions
- Obesity (Disorder)
- Keywords
- Obesity, Semaglutide, Tirzepatide, Energy balance, Energy expenditure, GLP-1 receptor agonist, dual GIP GLP-1 receptor agonist, Weight loss
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 31 Oct 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 28 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Take tirzepatide or semaglutide once weekly for 12 weeks
- Undergo identical baseline and week 12 study visits (including 24-hour whole room indirect calorimeter testing, MRI scan, body composition, 3-day meal plan and stool collection)
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideThis 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. |
| Tirzepatide | Experimental | Drug: TirzepatideThis 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age 18-60 years
- Body mass index (BMI) >30 kg/m2
- Stable body weight (<5kg change in the 3 months prior to screening)
Key exclusion criteria (20 listed)
- History of type 1 or type 2 diabetes or current diagnosis
- Glucose-lowering or weight loss drugs in the last 3 months or planned in the next 3 months
- Prior or planned bariatric surgery or planned low calorie meal program in the next 3 months
- Known clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction) or chronic GI symptoms (nausea, vomiting, diarrhea, constipation, bloating or unexplained abdominal pain) or chronically take drugs that directly affect GI motility
- Known liver disease other than non-alcoholic fatty liver disease, or ALT >3x ULN
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideThis 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 |
| SemaglutideThis 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 |
Primary outcome
24-hour Energy Expenditure Measured Using Whole Room Indirect Calorimetry
Time frame: Baseline, 12 Weeks
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.
7 secondary outcomes
Components of 24-hour Energy Expenditure (EE)
Time frame: Baseline, 12 Weeks
Energy Intake
Time frame: Baseline, 12 Weeks
Energy Extraction from Food
Time frame: Baseline, 12 Weeks
Brown Adipose Tissue (BAT) Activity
Time frame: Baseline, 12 Weeks
Appetite and Satiety
Time frame: Baseline, 12 Weeks
Stool Microbiota Composition
Time frame: Baseline, 12 Weeks
Body Composition
Time frame: Baseline, 12 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zubin Punthakee, MD, MSc principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tirzepatide and Semaglutide in people with Obesity (Disorder), run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Autumn Lawrence, MSc (905-525-9140 ext. 28083, joule3@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour Energy Expenditure Measured Using Whole Room Indirect Calorimetry (time frame: Baseline, 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.