GLP-1s to Enhance Lasting Optimal Weight

Eligibility 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
• * dependent on a cane or walker or needing assistance with any activity of daily living
• * history of mild cognitive impairment or dementia or cognitive impairment on Montreal Cognitive Assessment (MoCA score \<22)
• * evidence of depressive symptoms (Center for Epidemiologic Studies Depression scale score =\>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 for men)
• * 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 \>150 mins/week
• * severe arthritis, fracture, chronic injury, or other musculoskeletal disorder that prevents walking independently
• * joint replacement or other orthopedic surgery in past 6 months or planned in next 12 months
• * 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 repeated assessments
• * type 1 diabetes
• * uncontrolled type 2 diabetes (HbA1c \>7.5%), type 2 diabetes diagnosed within last year, 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 procedure within the past year; New York heart failure Class \>2; COPD requiring oxygen use; uncontrolled angina; PAD diagnosis within the last year; progressive neurologic disease (e.g., Parkinson's, ALS, MS); other diseases suggesting a life-expectancy \<3 years
• * personal or family history of medullary thyroid carcinoma, history of multiple endocrine neoplasia syndrome type 2, or any other cancer (except non-melanoma skin cancers) 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 including surgery 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 diabetes including 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