Recruiting
Phase 2

Tirzepatide

Sponsor:

Stanford University

Code:

NCT05912621

Conditions

Obesity

Overweight and Obesity

Overweight

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Interventions

Tirzepatide

Study Details

Brief summary:

Obesity, affecting 40% of US adults and costing 173b annually, represents a significant health care burden (1). It is associated with increased risk for multiple chronic diseases including hypertension, type 2 diabetes (T2D), cardiovascular disease, and NAFLD, as well as cancer, osteoarthritis, and obstructive sleep apnea. The investigators plan to test the hypothesis that tirzepatide, a dual GLP/GIP agonist, improves metabolic health (insulin resistance and regional fat distribution and cardiovascular risk profile) not only by inducing weight loss via GLP1-agonism, but also via beneficial cellular and molecular changes in adipose tissue, given that GIP binds receptors in human fat cells. Based on studies in mice showing that GIP alone or tirzepitide treatment decreases inflammation, increases lipid buffering (fat storage in the fat cells instead of releasing it into the bloodstream), and improves glucose homeostasis. The investigators believe that the GIP component of tirzepatide will make fat cells healthier and reverse lipotoxicity, which is one of the mechanisms by which obesity leads to insulin resistance, disordered regional fat distribution, and type 2 diabetes. To date, the effect of dual GLP1 and GIP agonist treatment on adipose tissue has not been evaluated in humans. Given the existing but limited data, dual GIP/GLP-1 agonist treatment in obese humans with metabolic risk factors is an attractive pharmacologic candidate that would lead to both weight loss and healthier fat, potentially offering uniquely powerful synergistic clinical benefits. It is thus of tremendous importance to define the biological effects of dual-agonist treatment on human adipose tissue structure and function, as well as related improvements in regional fat distribution and systemic adipose and muscle insulin sensitivity. In this study, the investigators will randomize overweight (with risk factors) or obese nondiabetic individuals to hypocaloric diet or tirzepatide for 22 weeks with matched weight loss for the first 6 weeks. The investigators will quantify insulin resistance, fat and lean mass, including regional fat distribution, and changes in adipose tissue (needle biopsy from abdominal fat tissue) to see if tirzepatide effects differ from dietary weight loss.

Conditions

Obesity

Overweight and Obesity

Overweight

Study ID

NCT05912621

Start date

Nov 9, 2023

Status verified date

Dec, 2024

Completion date

Dec, 2029

Anticipated

Primary completion date

Jun, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Inclusion Criteria:

  • nondiabetic as defined by fasting plasma glucose < 126 mg/dL while off all glucose lowering medications
  • BMI 27-39.9 kg/m2. Individuals with obesity (BMI 30-39.9 kg/m2) are not required to have an additional risk factor but those who are overweight (27-29.9 kg/m2) must have at least one weight-related factor as follows: hypertension defined as physician-diagnosed and taking antihypertensive medication or SBP> 130 or DBP > 80 mm Hg; dyslipidemia defined as physician diagnosed and taking medication or LDL > 160 mg/dL, TG > 150 mg/dL, HDL < 50 or < 40 mg/dL for women and men, respectively; prediabetes defined as fasting glucose 100-125 mg/dL off all antidiabetic or diabetogenic medications, physician diagnosed obstructive sleep apnea, non-alcoholic fatty liver disease, history of gallstones, and osteoarthritis.
  • Age 18-70
  • Pre and postmenopausal women will be eligible and details of last menstrual period and/or hormone replacement collected for statistical adjustment and formal testing for effect modification.

Exclusion Criteria:

  • prior bariatric surgery or liposuction
  • unstable body weight defined as self-reported weight change >2 kg over the past 6 weeks
  • unstable hypertension (defined as BP >160/100 mm Hg)
  • major organ disease
  • chronic inflammatory conditions
  • pregnancy/lactation
  • active malignancy undergoing treatment
  • use (current or within the past three months) of diabetogenic or weight loss medications, including GLP1 analogs
  • active eating or psychiatric disorder
  • heavy alcohol use (>2 drinks/day for women and > 3 drinks/day for men) will be excluded

Study Design

Enrollment

66 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 2.5 mg (up to 15 mg) Tirzepatide

Patients assigned to tirzepatide will undergo dose titration starting with 2.5 mg per day with an increase every four weeks if tolerated by nausea. During the first 6 weeks, weight loss must be matched with the dietary weight loss arm at 0.6 kg/week. Participants will be seen every two weeks to review diet and physical activity, evaluate tolerability/side effects, and obtain morning weight. If weight loss is greater than 0.6 kg/week, recommendations to increase caloric intake will be made through the week 6 visits that repeat baseline testings (biopsy, metabolic tests, and regional fat scans). After the 6th week, weight loss can occur naturally without any restrictions (no further matching to the dietary weight loss group is required). Starting at week 8 the visits are decreased to every 4 weeks. Biopsies, metabolic tests, and regional fat scans are completed at baseline, week 6, and end of study (week 22).

no intervention: Diet-controlled

The group assigned to dietary weight loss will undergo intensive dietary counseling with initial 3 day food diary evaluation followed by specific dietary recommendations that include macronutrient balanced, healthful and calorie-restricted diet, weekly dietitian visits, alternating between video and in person, use of a mobile app for food logging, weekly weights at home and biweekly weights, and review of these data by the study dietitian who will give individualized feedback at the weekly visits in order to attain targeted weight loss of 0.6 kg per week. The goal is to match weight loss in the tirzepatide and diet groups for the first six weeks. Any residual differences in weight loss at 6 weeks will be adjusted statistically. At six weeks all baseline tests (biopsy, metabolic tests, and regional fat scans) will be repeated, after which no further attempts for matching for weight loss will occur. At the end of the study (week 22), all baseline testing will occur again.

Interventions

Tirzepatide

Tirzepatide dose is titrated up by 2.5 mg every four weeks as per below, starting with 2.5 mg weekly and maxing out at 15 mg.

Primary outcome measure

  • Change in Adipocyte Size [ Time Frame: Baseline and Week 22 ]
  • Change in Adipocyte Fat Storage Capacity [ Time Frame: Baseline and Week 22 ]
  • Assess changes in Regional Fat [ Time Frame: Baseline, week 6, and week 22 ]
  • Change from baseline on the 2-stage Steady State Plasma Glucose test [ Time Frame: Baseline, week 6, and week 22 ]

Central Contacts and Locations

Central contacts

Nicole Turk, BS

6508880144nturk@stanford.edu

Locations

Clinical and Translational Research Unit

Recruiting

Palo Alto, California, United States, 94305

Contacts

Nicole Turk, BS

650-888-0144nturk@stanford.edu

Principal Investigator:

Tracey McLaughlin, MD

More Information

Sponsor

Stanford University

Last update posted

Dec 4, 2024

Last verified

Dec, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Stanford University on 2024-12-04.