The purpose of this study is to examine the effects of resistance exercise, such as weightlifting, on retention of muscle mass and mental health in individuals taking GLP-1 RAs (an obesity medication). Resistance exercise is focused on increasing the strength of participants' muscles, such as how much participant can lift.

•The duration of this study is 3 months. This includes:

• Orientation session to explain study protocol, exercise program, and complete questionnaire about participants' medical history and lifestyle.
• Two health assessments at baseline and at 3 months. These assessments include body composition, resting blood pressure, cardiovascular function, and muscular strength. Both the resistance exercise group and the control group will complete assessments at baseline and again at 3 months. After the 3-month period, individuals in the control group may choose to participate in the exercise training and complete the optional 6-month assessments.
• Personalized resistance exercise sessions for 60 minutes per session, twice per week, for 3 months.

• After the baseline assessment, if participants meet all eligibility criteria such as BMI, blood pressure, physical activity levels, and medication conditions, investigators will randomly assign participants to control group or resistance exercise group:

1. Control group: No resistance training during the first 3 months. After the 3-month period, participants may choose to participate in the optional exercise program, which includes 60 min/session, all for 2 sessions/week for 3 months. Participants may follow their provider's guidance for exercise except not to perform any strength or resistance training.

2. Resistance exercise group: 60 min/session, all for 2 sessions/week for 3 months.

   • Resistance exercise group (60 min/session): Each session will be 60 minutes of resistance, performing 3 sets of 8-20 repetitions (50-80% 1RM) of 11 exercises (chest press, lat pulldown, abdominal crunch, leg press, shoulder press, weighted row, leg extension, leg curl, chest fly, biceps curl, and triceps extension) using weight training machines.

Investigator will also ask participants to maintain their usual (pre-study) lifestyle physical activity outside of exercise sessions and to monitor participants' daily activity throughout the study period using pedometers and a lifestyle activity log.

Inclusion Criteria:

• Initiating GLP-1 RAs prescribed by physician or advanced practice practitioner and willing to withhold the start of the drug until baseline assessment completed
• Non-Smoker
• ≥18 years old
• Obese: Body Mass Index 30-45 kg/m² or BMI ≥27 + ≥1 weight related comorbidity; either hypertension or sleep apnea confirmed by participant self-report
• Inactive: not meeting the current US exercise guidelines over the past 6 months
• Capable of performing the required exercise training

Exclusion Criteria:

• A serious heart condition, such as unstable heart disease or heart failure, irregular heartbeats that are not well controlled, severe narrowing of the heart valves, or any recent inflammation of the heart or its lining
• Cancer requiring treatment in the past 5 years
• Hypothyroidism/hyperthyroidism
• Personal or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia Syndrome type 2 (MEN2)
• Gastroparesis
• Chronic/idiopathic acute pancreatitis
• Hepatic disease or cirrhosis
• Struggle with alcohol or other substance abuse (heavy drinking (≥4 drinks/day or ≥8 drinks/week for women; ≥5 drinks/day or ≥15 drinks/week for men), or who score ≥3 on the Drug Abuse Screening Test (DAST-10))
• Diabetes (Type 1 or 2)
• Major risk factors for coronary heart disease such as uncontrolled high blood pressure (≥160 mm Hg systolic or ≥100 mm Hg diastolic)
• Problems with your muscles or bones that limit your ability to exercise
• Any other medical condition that is life-threatening, can interfere with or be aggravated by the exercise training
• Plans to be away ≥2 weeks in the next 3 months
• Participation in any other concurrent interventional clinical trial
• History of eating disorders or weight-loss surgery, unstable weight (±5% change in past 6 months), or use of obesity medication (e.g., such as Wegovy, Ozempic, Saxenda, Zepbound, Mounjaro) in the last 3 months
• Inability to give informed consent
• History of major depression or other severe psychiatric disorders (e.g., who answer "yes" to question 9 on PHQ-9 in the Psych_QoL_Sleep questionnaires.)
• Pregnant or plan to become pregnant during study

Datasets will be available to outside researchers and public health professionals through the web sites of ClinicalTrials.gov and The Physical Activity Research Center (PARC) at the University of Pittsburgh. Outside researchers can learn what data are available and request a de-identified dataset (stripped of all personal health identifiers). All data requests will be discussed with the research team and approval will be obtained from the institutional review board overseeing the proposal of the data analysis project. Findings from the proposed study will also be published in peer-reviewed journals. The investigators seek to maximize the knowledge generated from this study by sharing data to expedite the translation of research into practice, with the goal of preserving lean body mass and improving quality of life.