LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy

At the mid-point of the thigh, investigators will measure the cross-sectional area of the quadriceps muscle and quantify muscle's thickness and size.

investigators will quantify intramuscular fat content

investigators will also assess liver fat using 3-D sequence (MR-Touch) magnetic resonance elastography (MRE

investigators will also assess liver stiffness using an IDEAL scan.

fat and fat free mass via Dual Energy X-ray Absorptiometry (DEXA)

Grip strength will be measured 3 times in each hand using a Jamar dynamometer.

The number of chair rises completed in 30 seconds measured.

Habitual gait speed will be measured during a 4 metre walk test

Aerobic fitness will be quantified with the 6 min walk test.

investigators will measure aspartate amino transferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP), gamma-glutamyltransferase (GGT) and bilirubin.

investigators will assess kidney function by estimating the glomerular filtration rate (eGFR).

investigators will assess participants' lipid profiles by measuring the concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and total cholesterol.

Fibrosis-4 (FIB-4) Index score will be calculated using liver function test parameters, including age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The FIB-4 index is a continuous score used to estimate the degree of liver fibrosis. There is no fixed minimum or maximum value; however, higher scores indicate more advanced liver fibrosis and therefore a worse outcome.

investigators will assess participants' inflammatory profiles by measuring the circulating levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor-alpha (TNF-α).

An oral glucose tolerance test will be performed with a cannula inserted and a baseline blood sample collected, a 75g glucose load consumed and further samples collected at 15, 30, 60 90 and 120 min. Samples will be analysed for glucose and insulin levels.

Participants will complete International Physical Activity Questionnaire (IPAQ) which measures physical activity across multiple domains (e.g., work, transport, domestic, and leisure activities). The IPAQ provides a continuous score expressed in Metabolic Equivalent of Task (MET)-minutes per week.

The total score has no fixed minimum or maximum value; higher scores indicate higher levels of physical activity, and therefore represent a better outcome (greater physical activity).

Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a validated questionnaire that evaluates sleep quality and sleep disturbances over a 1-month period. The PSQI generates a global score ranging from 0 to 21, where higher scores indicate poorer sleep quality (worse outcome).

Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). This standardized instrument measures health status across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted into a single utility index score.

The EQ-5D-5L index score typically ranges from less than 0 (states worse than death) to 1 (full health), where higher scores indicate better health-related quality of life (better outcome).

Baseline dietary intake will be assessed using the EatWellQ8 Food Frequency Questionnaire (FFQ), a validated dietary assessment tool for the Kuwaiti population. The FFQ is used to estimate habitual dietary intake across food groups and nutrients over a defined recall period.

The questionnaire generates continuous estimates of dietary intake based on reported frequency of consumption of food items and standard portion sizes (grams). There is no fixed minimum or maximum score. Higher values indicate greater consumption of the corresponding food or nutrient, with interpretation dependent on the specific dietary component being analyzed.

Baseline carbodhyrate, fat and protein intake (all g/day) will be quantified by the use of the EPIC food frequency questionnaire and multi-pass 24h recall. Further 24h recalls will be carried out at 0.5,1,3 and 6 months of the follow up period.

Activities of daily living will be assessed using the Barthel Index of Activities of Daily Living, a validated scale that measures functional independence in personal care and mobility tasks (e.g., feeding, bathing, grooming, dressing, bowel and bladder control, toileting, transfers, mobility, and stair climbing).

The Barthel Index generates a total score ranging from 0 to 100, where higher scores indicate greater independence in activities of daily living (better outcome), and lower scores indicate greater dependency (worse outcome).

Concomitant medication use will be assessed by systematic documentation of all medications taken by participants throughout the study period, including prescription medications, over-the-counter drugs, and dietary supplements. Data will be collected at each study visit through structured participant interviews and review of medical records.

Medications will be recorded descriptively and categorized by therapeutic class, dose, frequency, and duration of use.