Actively Recruiting
Tirzepatide: Reversal of Lipotoxicity and Adipose Tissue Dysfunction in Humans With Overweight/Obesity
Led by Stanford University · Updated on 2024-12-04
66
Participants Needed
1
Research Sites
316 weeks
Total Duration
On this page
Sponsors
S
Stanford University
Lead Sponsor
E
Eli Lilly and Company
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
Official Title
Tirzepatide: Reversal of Lipotoxicity and Adipose Tissue Dysfunction in Humans With Overweight/Obesity
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Nondiabetic with fasting plasma glucose less than 126 mg/dL and not on glucose lowering medications
- Body mass index (BMI) between 27 and 39.9 kg/m2
- For overweight individuals (BMI 27-29.9), at least one weight-related risk factor such as hypertension, dyslipidemia, prediabetes, obstructive sleep apnea, non-alcoholic fatty liver disease, history of gallstones, or osteoarthritis
- Aged 18 to 70 years
- Pre- and postmenopausal women are eligible with menstrual or hormone replacement details collected
You will not qualify if you...
- Prior bariatric surgery or liposuction
- Unstable body weight with weight change greater than 2 kg in the past 6 weeks
- Unstable hypertension with blood pressure above 160/100 mm Hg
- Major organ disease
- Chronic inflammatory conditions
- Pregnancy or lactation
- Active cancer undergoing treatment
- Use of diabetogenic or weight loss medications, including GLP1 analogs, currently or within past 3 months
- Active eating disorders or psychiatric disorders
- Heavy alcohol use defined as more than 2 drinks per day for women or more than 3 drinks per day for men
AI-Screening
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Trial Site Locations
Total: 1 location
1
Clinical and Translational Research Unit
Palo Alto, California, United States, 94305
Actively Recruiting
Research Team
N
Nicole Turk, BS
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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