GLP-1s to Enhance Lasting Optimal Weight

Prior treatment

• joint replacement or other orthopedic surgery in past 6 months or planned in next 12 months
• use of oral steroids for \>1 month within the last 3 months

Other illness

• history of mild cognitive impairment or dementia or cognitive impairment on Montreal Cognitive Assessment (MoCA score \<22)
• history of binge eating disorder
• severe arthritis, fracture, chronic injury, or other musculoskeletal disorder that prevents walking independently
• uncontrolled hypertension (systolic \>160 OR diastolic \>100 mmHg) upon repeated assessments
• type 1 diabetes
• 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
• 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
• 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

Lab values

• 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

Age

• 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

Other

• dependent on a cane or walker or needing assistance with any activity of daily living
• 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
• regular participation in high intensity aerobic or resistance exercise training \>150 mins/week
• osteoporosis (self report or DXA t-score \<= -2.5 on total hip and/or femoral neck)
• overnight hospitalization within the past 6 months
• current participation in another intervention research study
• planned out of town trips greater than 3 weeks in the next year

• 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