Age: 45 - 70+
Healthy Volunteers: Not accepted
Inclusion Criteria:
1. Gender: men and women
2. Ethnicity: all ethnic groups
3. Age between 45 and 75 years
4. BMI ≥ 30 kg/m2 and BMI < 45 kg/m2
5. Diagnosis of Type 2 Diabetes (T2D) with HbA1c levels between 7% and 10.5%.
6. Starting subcutaneous semaglutide for clinically indicated T2D management.
7. Ability and willingness to participate in the study for its full duration.
8. Provision of informed consent for participation in research.
Exclusion Criteria:
1. Previous intolerance or allergy to any semaglutide-based therapy.
2. History of prior intolerance to any GLP-1RA or GIP/GLP-1RA.
3. Unwillingness or uncertainty to commit to the duration of the study.
4. Contraindication to MRI (e.g. claustrophobia, implanted devices including cardiac pacemaker and cardioverter-defibrillators), circumference of largest calf > 17inch/43cm (max size to fit into the MR coil).
5. History of myocardial infarction or coronary revascularization (percutaneous intervention or coronary artery bypass) within 30 days prior to screening.
6. History of hospitalization for heart failure within the past 30 days, or NYHA class IV
7. Current use of glucocorticoid therapy (≥5 mg prednisone or equivalent).
8. Self-reported weight loss > 10 lbs in the 90 days prior to screening.
9. Use of other mediation, on or off-label, for the primary intent of weight loss within 90 days prior to screening.
10. Secondary etiologies for sarcopenia (e.g., gastrointestinal malabsorption, myopathies, severe neurological conditions).
11. Glomerular Filtration Rate (eGFR) within the past 120 days is not available.
12. Mental incapacity or language barriers preventing informed consent and compliance.
13. Pregnancy, plans for pregnancy in the next 12 months, or lactating/nursing females.
14. History of bariatric or metabolic surgery or related procedures.
15. Prior participation in the Endocrinology and Metabolism Institute's Integrated Weight Management Program within the past 3 months.
16. Active smoking.
17. Excessive alcohol consumption, defined as ≥3 drinks per day.
18. Uncontrolled lung disease (e.g., severe asthma or COPD).
19. Uncontrolled thyroid disease.
20. Personal commitments that may limit optimal participation (e.g., work, travel, caregiving responsibilities).
21. History of malabsorptive disorders, such as celiac disease or Crohn's disease.
22. Cholestatic liver disease or inadequate hepatic function (AST/ALT > 3.0 x ULN).
23. Liver cirrhosis.
24. Conductive implanted devices (e.g., cardiac pacemaker, cardioverter-defibrillators).
25. Major surgical procedures or significant traumatic injury within 30 days prior to the enrollment date.
26. Any medical or surgical condition that, in the opinion of the principal investigator, may make the participant unfit for the trial (e.g., psychiatric disorders, malignancy).
27. Any condition, unwillingness, or inability, not otherwise covered by exclusion criteria, which might jeopardize the subject's safety or compliance with the protocol.
28. Presence of metal in the eye