Recruiting
Phase 4

Tirzepatide vs. Semaglutide

Sponsor:

McMaster University

Code:

NCT07900074

Conditions

Obesity (Disorder)

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

Tirzepatide

Semaglutide

Study Details

Brief 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. 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)

Conditions

Obesity (Disorder)

Study ID

NCT07900074

Start date

Oct 31, 2026

Status verified date

Oct, 2026

Completion date

Dec 31, 2029

Anticipated

Primary completion date

Dec 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not 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

Study Design

Enrollment

80 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Semaglutide

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.

experimental: 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.

Interventions

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.

Semaglutide

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.

Primary outcome measure

  • 24-hour Energy Expenditure Measured Using Whole Room Indirect Calorimetry [ Time Frame: Baseline, 12 Weeks ]

Central Contacts and Locations

Central contacts

Autumn Lawrence, MSc

905-525-9140joule3@mcmaster.ca

Aaron Thomas, PhD

905-525-9140joule3@mcmaster.ca

Locations

McMaster University

Recruiting

Hamilton, Ontario, Canada, L8S 4L8

Contacts

Autumn Lawrence, MSc

289-251-2187lawrea8@mcmaster.ca

Aaron Thomas, PhD

605-525-9140thomasac@mcmaster.ca

Principal Investigator:

Zubin Punthakee, MD, MSc

More Information

Sponsor

McMaster University

Last update posted

Oct 28, 2026

Last verified

Oct, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-29. This information was provided to ClinicalTrials.gov by McMaster University on 2026-10-28. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.