GLP-1s to Enhance Lasting Optimal Weight

Inclusion Criteria:

• BMI 30-37 kg/m2 or BMI 27-<30 kg/m2 with at least 1 weight-related comorbidity

• community dwelling

• able to provide own transportation to study visits

• willing to provide informed consent

• willing to take terzepatide for 9 months

• agree to all study procedures/assessments

• approved for participation by the study physician

Exclusion Criteria:

• dependent on a cane or walker or needing assistance with any activity of dailyliving

• history of mild cognitive impairment or dementia or cognitive impairment on MontrealCognitive Assessment (MoCA score <22)

• evidence of depressive symptoms (Center for Epidemiologic Studies Depression scalescore =>16

• use of >1 tobacco product/day or 4/week or vaped >1/week in past year

• excessive alcohol use in past month (>7 drinks/week for women; >14 drinks/week formen)

• weight loss or gain >5% in past 3 months

• vegan or other severe dietary restriction

• history of binge eating disorder

• regular participation in high intensity aerobic or resistance exercise training >150mins/week

• severe arthritis, fracture, chronic injury, or other musculoskeletal disorder thatprevents walking independently

• joint replacement or other orthopedic surgery in past 6 months or planned in next 12months

• osteoporosis (self report or DXA t-score <= -2.5 on total hip and/or femoral neck)

• uncontrolled hypertension (systolic >160 OR diastolic >100 mmHg) upon repeatedassessments

• type 1 diabetes

• uncontrolled type 2 diabetes (HbA1c >7.5%), type 2 diabetes diagnosed within lastyear, or newly identified type 2 diabetes (HbA1c >6.5%)

• dialysis or abnormal kidney function (eGFR <30 ml/min/1.73m2)

• liver disease or abnormal liver function (ALT levels 2 times above normal limit)

• severe anemia (Hb <11 g/dL)

• potassium or sodium above or below normal limits

• uncontrolled thyroid disease (hypo/hyper) or requiring recent (past 3 months)adjustments in thyroid hormone supplementation or TSH <0.45 or >4.5 mU/L

• stroke, heart attack, heart failure hospitalization, or revascularization procedurewithin the past year; New York heart failure Class >2; COPD requiring oxygen use;uncontrolled angina; PAD diagnosis within the last year; progressive neurologicdisease (e.g., Parkinson's, ALS, MS); other diseases suggesting a life-expectancy <3years

• personal or family history of medullary thyroid carcinoma, history of multipleendocrine neoplasia syndrome type 2, or any other cancer (except non-melanoma skincancers) requiring treatment in past year

• history of gastroparesis or pancreatitis

• cholelithiasis, severe irritable bowel syndrome or Crohn's disease

• history of stomach or small intestinal surgery (except appendectomy but includingsurgery for weight loss)

• recent (within 4 weeks) acute respiratory illness including influenza, COVID-19

• overnight hospitalization within the past 6 months

• regular use of growth hormones, medications prescribed for weight management,prescription osteoporosis medications, certain prescription medications for diabetesincluding insulin, sulfonylurea, meglitinides, GLP-1 agonists, SGLT2 inhibitors

• use of oral steroids for >1 month within the last 3 months

• current participation in another intervention research study

• planned out of town trips greater than 3 weeks in the next year