GLP-1s to Enhance Lasting Optimal Weight

This study will enroll 40 older adults with obesity (or overweight with a weight-related comorbidity) in a 9-month pilot to examine the effects of tirzepatide on body composition, bone health, and physical performance. All participants will receive tirzepatide, 5 mg per week and counseling sessions (group and individual) on diet quality and physical activity as well as behavioral strategies to facilitate dietary and physical activity changes. Participants will be expected to weigh themselves daily on a smart scale, record their food and beverage consumption, and keep track of daily step counts over the 9-month intervention period. Body composition, bone health, and physical performance will be measured at baseline prior to intervention and approximately nine months later. This data will be used to examine the effects of tirzepatide on total and appendicular lean and total fat mass measured by DXA; hip and spine bone mineral density measured by DXA; and leg strength and physical performance (expanded Short Physical Performance Battery, 400-m walk).

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 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