Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: Recovery Effects After Semaglutide Termination

Inclusion Criteria:

• Men and women with previously diagnosed BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 andadiposity-related complications (such as osteoarthritis, nonalcoholic liver disease,sleep apnea, and hypertension) without preexisting cardiovascular disease or type 2diabetes.

• Age 18 - 75 years inclusive

• Ongoing weight-loss treatment consisting of weekly subcutaneous semaglutide atminimum dose of 1 mg/weekly with documented weight reduction of at least 10% ofpre-treatment body weight

• Stable weight over past 12 weeks (less than 5% change in body weight) (self-reported)

• Ability to read and understand English

Exclusion Criteria:

• Previously diagnosed cardiovascular disease defined as previous myocardialinfarction, previous stroke, or symptomatic peripheral arterial disease.

• Currently pregnant or lactating

• Previously diagnosed type 2 diabetes

• Use of any other pharmacological treatment for weight-loss

• Previous surgical treatment for weight loss such as gastric bypass or gastric band

• Any history of eating disorder

• Renal dysfunction as evidenced by estimated glomerular filtration rate < 25 ml/minby CKD-EPI Creatinine Equation

• New York Heart Association class II-IV heart failure

• Hepatic disease considered to be clinically significant (includes jaundice, chronichepatitis, or previous liver transplant) or transaminases >2.5X the upper limit ofnormal

• Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapywithin the previous 5 years (with the exception of basal cell skin cancer)

• Personal or family history of medullary thyroid carcinoma or in patients withMultiple Endocrine Neoplasia syndrome type 2

• Any other factor likely to limit adherence to the study, in the opinion of theinvestigators