Tirzepatide in PWS, HO and GNSO

This research study is comparing the effectiveness of a weight loss medication called Tirzepatide in young adults with Prader-Willi Syndrome and/or hypothalamic obesity, as compared to young adults with obesity that is unrelated to a genetic syndrome or underlying medical cause. These groups will be given medication for 1 year to see how weight and other health factors are effected by the medication.

This study is for the following individuals:

* Age 18-26.
* Have Prader-Willi Syndrome, Hypothalamic Obesity, or Obesity unrelated to a genetic syndrome or medical condition.
* Have a BMI in the obesity range

If you/your child decide to take part in the research study, you/your child would participate in the study for approximately 56-60 weeks. During this time the following can be expected:

* Receive tirzepatide for once-weekly dosing.
* Complete 6 in-person SCH study visits
* Complete 4 telehealth visits.
* Complete the following research procedures:

  * Medical Record Review
  * Vital Signs
  * Anthropometry (e.g., height, weight, waist measurements)
  * Physical Exams
  * Laboratory Tests (e.g., fasting blood draws, urine test)
  * Dual-Energy Absorptiometry (DXA) scans
  * Questionnaires

Eligibility Criteria:
Inclusion Criteria:

* Individuals 18-26 years with a BMI in the obesity range (BMI ≥95th percentile for age and sex or ≥30 kg/m2) with either 1) genetically confirmed diagnosis of PWS, 2) hypothalamic obesity as defined by damage to the medial hypothalamic region resulting in dysregulation of satiety and energy balance as diagnosed by a physician, 3) general obesity unrelated to a genetic syndrome or underlying medical condition
* In a stable care setting at least 6 months prior to enrollment
* Able and willing to participate in study visits including tolerating blood draws, urine samples and tolerate DXA scan.
* Ability to take weekly subcutaneous tirzepatide
* Consistent caregiver if they are not independent
* Stable diet and exercise regimen for at least 6 months prior to enrollment
* Able to use contraceptive methods if able to conceive offspring in order to prevent unintentional pregnancy during the study

Exclusion Criteria:

* Current or recent (within 3 months of start of study drug initiation) use of weight loss medications
* Current use of insulin or sulfonylurea or other medication affecting insulin secretion or GLP1 clearance
* Current or prior use of any GLP1A or DPP4 inhibitor during the 6 months before screening
* Any medications that may affect the study endpoints
* Significant weight change (\>3% weight gain or loss) in the last 2 months prior to enrollment
* Change in dose of chronic endocrine medications (testosterone, estrogen, levothyroxine, or growth hormone medications) \>10%/kg/day for at least 3 months prior to study
* Current pregnancy or desire to become pregnant within study period, current lactation
* History of recurrent pancreatitis, CKD, gastroparesis
* Chronic/acute heart, kidney, or liver disease
* Personal or family history of medullary thyroid carcinoma or MEN syndrome type 2
* Uncontrolled diabetes (A1C \>8.5%)
* DVT
* Cancer within the previous 5 years
* Current participation in an interventional clinical study
* Previous or planned surgical treatment for obesity
* Individuals with current substance abuse equivalnt to moderate or severe based on DSM 5 criteria (Hasin DS, 2013)
* Any suicidal ideation in the past year
* Unable to perform any of the procedures for the study
* Have a body weight, height, and/or width that that prohibits the ability to obtain accurate measurements according to the DXA manufacturer's specification
* Any condition that would prevent successful participation in the study.