JOULE3

RecruitingPhase 4

Mechanisms of Weight Loss: Tirzepatide vs Semaglutide

Mechanisms of Weight Loss Due to Dual GIP GLP-1 Receptor Agonism With Tirzepatide Compared to Semaglutide: A Randomized Controlled Trial

Lead sponsor

McMaster University

Assets

Semaglutide / Tirzepatide

Listed sites

Recruiting sites

Estimated enrollment

Study population

Obesity / overweight

Eligibility highlights

•BMI ≥30

Primary endpoint

•24-hour Energy Expenditure Measured

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07900074

Org study ID19795

Timeline

Milestones

Study first posted2026-10-28actual

Last update posted2026-10-28actual

Study start2026-10-31estimated

Primary completion2029-12-31estimated

Study completion2029-12-31estimated

Assets

Investigational agents

Semaglutide Tirzepatide

Who this study enrolls

Obesity / overweight

Who can enroll

Minimum age18 Years

Maximum age60 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age 18-60 years

•Body mass index (BMI) >30 kg/m2

•Stable body weight (<5kg change in the 3 months prior to screening)

Exclusion criteria

•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

•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

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Weight & body composition

2 endpoints

Secondary/protocol endpoint

Brown Adipose Tissue (BAT) Activity

Time frame:Baseline, 12 Weeks

descriptive

Secondary/protocol endpoint

Body Composition

Time frame:Baseline, 12 Weeks

descriptive

Other (unclassified)

6 endpoints

Primary/protocol endpoint/low confidence

24-hour Energy Expenditure Measured Using Whole Room Indirect Calorimetry

Time frame:Baseline, 12 Weeks

descriptive