Can a High-Protein diet and weight training prevent muscle loss while on Weight-Loss drugs?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age 30- 60 years * BMI 27.0-37.0 kg/m² at screening * English speaking (at this time, MyNetDiary, a food-logging app used for tracking protein-intake, is only set up for English, and our RDN is only capable of providing nutritional counseling in English) * Received a prescription for tirzepatide, a second-generation oral or injectable dual GIP/GLP-1 receptor agonist (Zepbound/Mounjaro) that is FDA-approved for obesity; and * Has not yet started tirzepatide and agrees to complete a 4-week run-in period at the initial dose with \<3% weight loss from baseline; OR * Has initiated tirzepatide and is within the first 4 weeks at the initial dose with \<3% weight loss from pre-treatment baseline. * On a stable regimen for major chronic conditions (e.g., antihypertensives, lipid-lowering agents, oral antidiabetics, hypothyroidism) for ≥ 8 weeks prior to enrollment. * Willing and able to: * (i) Receive high-protein diet counseling and attempt to achieve \~2.5 g/kg FFM /day protein; * (ii) Attend scheduled nutrition telehealth visits with an RDN; * (iii) Medically cleared for moderate-intensity resistance training 2 days/week (no condition that would preclude safe participation in either diet-only or diet plus resistance training). * Willing and able to undergo whole-body MRI at baseline and 6 months without sedation. * Able to understand procedures and provide written informed consent in English (at this time, MyNetDiary, a food-logging app used for tracking protein-intake, is only set up for English, and our RDN is only capable of providing nutritional counseling in English) Exclusion Criteria: * Patients currently prescribed oral or injectable incretin mimetics containing GLP-1RAs, including Exenatide, Liraglutide, Lixisenatide, Dulaglutide, Semaglutide. Participants who are currently prescribed tirzepatide and have been using for \>4 weeks will also be excluded. * Prior use of incretin mimetics containing GLP-1RAs with \>3% weight loss in a 4-week period * Lost \>5% body weight in the past 6 months * Has consistently resistance trained (\>10 sessions) in the last year * Currently taking medication or supplements that have been shown to impact muscle function and muscle mass in the last 6 months * Participants who live outside of the tri-state area and/or are not willing to come to New York City for in-person visits outlined * Plans to be out of town more than 2 consecutive weeks or \>6 weeks total over the next 6 months * Type 1 or 2 diabetes; uncontrolled diabetes (e.g., HbA1c \> 6.4% if specified); recurrent severe hypoglycemia or hypoglycemia unawareness. * Moderate-to-severe chronic kidney disease (e.g., eGFR \< 45-60 mL/min/1.73 m2 final cutoff per protocol) or other renal disease * Decompensated cirrhosis, severe chronic liver disease, or active liver disease * Unstable cardiovascular disease (e.g., myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina or decompensated heart failure (HF) within \<6 months) * Active malignancy requiring systemic therapy in the past 6-months (excluding non-melanoma skin cancer) * Serious medical/psychiatric conditions making participation unsafe or likely to impair adherence * Pregnant, planning pregnancy within 6 months, or breastfeeding; women of childbearing potential unwilling to use effective contraception per institutional/drug-label guidance. * Conditions requiring protein restriction (e.g., advanced Chronic Kidney Disease (CKD), relevant inborn errors of metabolism). * Severe, poorly controlled gout/hyperuricemia * Significant GI disease impairing tolerance or absorption (e.g., active Inflammatory Bowel Disease (IBD) with frequent flares, short bowel syndrome, severe gastroparesis beyond expected GLP-1 effects) * Severe food allergies or intolerances that preclude a high-protein diet or ingestion of whey or pea protein and associated additives/ingredients of the protein powders used in this study. * Has or previously had an eating disorder * Severe musculoskeletal, neuromuscular, or other conditions that preclude moderate-intensity RT * Advised not to exercise by their general practitioner or medical professional or refusal to obtain medical clearance if indicated by Physical Activity Readiness Questionnaire (PAR-Q) answers * Standard contraindications to MRI: tattoos with metallic ink, pacemaker, cerebral and/or cochlear implant, metal in the eye, severe claustrophobia, presence of electronic devices or ferromagnetic metallic foreign or implanted objects that could constitute a hazard, inability to lie flat, or any other contraindication for MRI. * Weight \>200kg, or large body habitus which the MRI scanner cannot accommodate. * Inability or unwillingness to attend a reasonable proportion of RT sessions and refusal of accommodations * Concurrent enrollment in another weight management intervention * Prior bariatric surgery within the past 12 months or planned bariatric surgery within the 6-month study period. * Active alcohol or drug use disorder * Significant cognitive impairment or language barrier precluding informed consent or adherence * Any reason that could compromise the participants' safety, based on the judgment of the investigators and/or clinical coordinators.