Tirzepatide Impact Assessment Study

This prospective non-randomized comparative pilot study is conducted at the Nutrition and Metabolic Health Initiative (NMHI) clinic at Texas Tech University in Lubbock, Texas. The study includes two arms: a GLP-1 receptor agonist (GLP-1 RA) arm and a lifestyle (LS) comparator arm. GLP-1 RA arm participants are recruited from obesity medicine and aesthetics clinics in Lubbock, Texas, and enrolled within 0 to 3 days of initiating semaglutide or tirzepatide as prescribed by their own medical provider. LS comparator arm participants are recruited from the community via flyers, community events, hospital intranet postings, and university listservs; they will receive a structured behavioral intervention at no cost.

Each arm follows a two-visit assessment schedule at baseline and at three months. In-person visits include anthropometric measurement, bioelectrical impedance analysis for body composition, resting metabolic rate assessment via MedGem indirect calorimetry, blood pressure measurement (average of two readings after a five-minute rest), and venipuncture for biological sample collection. Blood is drawn into serum-separating tubes and an EDTA tube. Serum is processed for lipid panels, basal metabolic panels, hepatic and renal function markers including alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine, as well as appetite-related hormones including ghrelin, GLP-1, insulin, leptin, and peptide YY. The EDTA tube is processed for whole-blood RNA sequencing and untargeted metabolomics. Participants also wear a Garmin device for two weeks following the baseline visit to monitor sleep, heart rate, and oxygen saturation. Online questionnaires are completed via Qualtrics prior to each in-person visit.

LS comparator participants receive three individual lifestyle education sessions across the study period: at baseline, at one month, and at two months. Sessions may be completed in person or via a HIPAA-secured video platform and last approximately 30 to 45 minutes each. Each participant's total energy expenditure (TEE) is estimated by multiplying measured resting metabolic rate by a physical activity factor. Participants are instructed to follow a 500 kilocalorie daily deficit from TEE and to accumulate 150 to 300 minutes of moderate-intensity physical activity per week. Meal plans are based on the Academy of Nutrition and Dietetics Nutrition Care Manual. Dietary and physical activity adherence is monitored using MyFitnessPal or a food journal, with records reviewed at each session.

Given the pilot nature of this study, the primary emphasis is on effect size estimation and variance characterization to inform future adequately powered trials rather than definitive hypothesis testing. For example, with 12 participants in the GLP-1 receptor agonist arm and 15 participants in the LS comparator arm, the study is powered to detect only large between-group differences in cardiometabolic outcomes. Transcriptomic and metabolomic findings should be interpreted as hypothesis-generating. IRB approval was obtained prior to study initiation (IRB Number: IRB2024-370).

Inclusion criteria

• Age 18 years or older
• BMI of 27.5 kg/m2 or higher
• For GLP-1 RA arm: initiating semaglutide or tirzepatide for weight loss as prescribed by their own medical provider
• For LS comparator arm: not currently taking a GLP-1 receptor agonist or other weight-loss medication, and no use of weight-loss medication within the past 3 months

Exclusion criteria

• Pregnant
• Breastfeeding
• Wears a pacemaker or other internal medical device
• Chronic kidney disease in the past 2 years
• Active cancer or cancer treatment within the past 6 months
• Current diagnosis of any major endocrine, inflammatory, cardiovascular, or neurological disorder/condition, including Addison's disease, autism, congestive heart failure, Crohn's disease, Cushing's syndrome, hyperparathyroidism, multiple sclerosis, neuromuscular disorders (Guillain-Barre syndrome or myasthenia gravis), stroke, thyroid gland disorders (hyperthyroidism or hypothyroidism), type 1 diabetes, and ulcerative colitis
• Insulin therapy for type 2 diabetes
• For LS comparator arm only: initiating any weight-loss medication (including a GLP-1 receptor agonist) currently or within the past 3 months