Role of Caveolin 1 (CAV-1) Deficiency in Response to Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Treatment

Summary

Obesity has become an important public health issue that leads to insulin resistance, diabetes, hypertension, dyslipidemia, and cardiovascular diseases. Although weight loss with calorie restriction and increased physical activity improve these complications, many people fail these lifestyle interventions. Therefore, pharmacologic agents have been used for weight management in addition to lifestyle interventions. In the past few years, one of the widely used pharmacologic agents for weight management is Glucagon-like peptide 1 receptor agonists (GLP1 RAs). Overall, this class of medications improves both metabolic and cardiovascular profiles while causing weight loss, but their effects can vary between individuals. Therefore, it is essential to understand who will respond best to this therapy. Based on previous research on the interaction between a cell membrane molecule, caveolin-1, and glucagon-like peptide 1 receptor, we hypothesize that genetic variations in the caveolin-1 gene explain the variable cardiometabolic responses.

Eligibility

Inclusion Criteria:

* Age ≥18 years, body mass index (BMI) ≥30.0 kg/m2 or ≥27.0 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, prediabetes, dyslipidemia, obstructive sleep apnea,
* Normal screening laboratory values,
* Systolic BP \< 160 mmHg and diastolic BP \< 95 mmHg as determined from measurement during screening, using a random-zero device in the clinic and normal electrocardiogram, use of anti-hypertensive medications will be allowed except for mineralocorticoid receptor antagonists.

Exclusion Criteria:

* Diabetes mellitus,
* Treatment with a glucose-lowering agent(s) or anti-obesity medication within 90 days of screening,
* Treatment with a GLP-1 receptor agonist within 180 days,
* Current treatment with beta-blocker, or steroids,
* Pregnancy,
* Personal history of pancreatitis,
* Personal history of cholelithiasis,
* Previous surgical obesity treatment,
* Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma,
* Medical illness other than hypertension, prediabetes, obstructive sleep apnea, or dyslipidemia,
* Alcohol intake \>12 oz. per week,
* Tobacco, or recreational drug use

Conditions2

Locations1 site

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