Obesity
Conditions
Keywords
Body composition, pharmacologically induced weight loss, GLP-1 receptor agonists, muscle mass, dietary protein
Brief summary
This study investigates how weight-loss medications, specifically GLP-1 receptor agonists, affect body composition, with a special focus on preserving muscle mass in adults with obesity. While these medications are highly effective for weight loss, they can sometimes lead to an unwanted loss of valuable muscle mass (a condition that can lead to sarcopenia). To explore how to prevent this, researchers are conducting a 3- to 6-month randomized controlled trial involving adults aged 30 to 65 years with a BMI greater than 30 kg/m². Participants who are receiving GLP-1 medications will be randomly assigned to one of two groups: one group will receive the standard medication treatment alone, while the other group will receive the medication along with specific dietary guidance focused on increasing daily protein intake.
Detailed description
Obesity is a global public health challenge. While weight loss is essential, preserving Muscle Mass (MM) is crucial for maintaining metabolic health, functional capacity, and long-term treatment outcomes. Although Glucagon Like Peptide- 1 Receptor Agonists (GLP-1 RAs) are highly effective for weight reduction, significant loss of lean mass raises concerns regarding sarcopenic obesity, especially in vulnerable populations. Muscle tissue is metabolically active; its loss can also reduce resting energy expenditure, potentially leading to weight regain post-treatment. Current guidelines emphasize the synergy between pharmacological treatment and lifestyle interventions. High dietary protein intake is hypothesized to mitigate MM loss by stimulating muscle protein synthesis and enhancing satiety. However, existing research often fails to distinguish between Fat-Free Mass (FFM) and Skeletal Muscle Mass (SMM), leaving a gap in our understanding of true muscle preservation during intensive weight loss. The primary aim of this research is to address a critical gap in literature by evaluating the combined effect of GLP-1RAs and dietary protein on MM preservation. By synthesizing current research findings, we seek to provide a better understanding of how these agents influence fat and lean tissue distribution, thereby informing clinical practices and guiding future research directions in obesity and diabetes management using GLP-1 RAs. Specifically, the research aims to: 1. Assess the impact of GLP-1 RAs on body composition: It is expected that the treatment will lead to weight loss and a reduction in Fat Mass (FM), but its effect on MM will vary. 2. Evaluate the role of protein in attenuating MM loss compared to pharmacological treatment alone: The hypothesis is that combining high-protein intake with GLP-1 RAs will better preserve or even increase MM during weight loss, compared to GLP-1 treatment alone. 3. Investigate long-term maintenance: Determine if COM-B-Model-led nutritional changes lead to superior weight maintenance 12 months post-intervention. This study could lead to more tailored and effective treatments for adults with obesity seeking to lose weight without sacrificing MM and also to explore better practices regarding the currently challenging phase after weight loss, which is maintenance.
Interventions
BEHAVIORALHigh Protein Dietary Intervention
Individualized dietary guidelines focusing on increased protein consumption to preserve muscle mass during weight loss.
BEHAVIORALControl (Standard Mediterranean Diet Counseling)
Standard nutritional counseling based on the Mediterranean diet pattern as part of usual clinical practice.
Sponsors
Hellenic Mediterranean University
University General Hospital of Heraklion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults 30-65 years old * BMI: ≥30 kg/m² * Signed Informed Consent
Exclusion criteria
A. Metabolic and Medical Conditions: * Uncontrolled type 2 diabetes (HbA1c \> 9.0%) * Known cardiovascular disease (e.g., coronary artery disease, heart failure NYHA 3-4) * Chronic kidney disease stage 4-5 (GFR \<60 ml/min) * Liver disease (known hepatitis, ALT ≥ 3 or total bilirubin ≥ 2 times ULN) * Inflammatory bowel disease * Celiac disease * History of pancreatitis * Any disorder potentially causing malabsorption * Active cancer or history of malignancy within the past 3 years * Psychiatric disorders affecting adherence or assessment B. Medication and Supplement Use * Chronic use of medications affecting metabolism or body composition (e.g., corticosteroids, anti-obesity drugs) * Use of anti-inflammatory or antioxidant medications * Use of probiotics, prebiotics, or laxatives within the last month * Unstable medication regimen (changes within the past 3 months) * Use of protein and creatine supplements. C. Dietary and Lifestyle Factors: * Alcohol or substance abuse * Engagement in intense regular physical activity D. Reproductive Status: * Pregnancy or breastfeeding * Pregnancy within the past 12 months * Plans to become pregnant during the study E. Other: \- Any condition that, in the opinion of the Investigator, may interfere with participation, adherence, or the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Muscle Mass | Baseline and End of Intervention (up to 24 weeks) | Evaluation of the change in Muscle Mass using a multi-compartment body composition model (4C/5C). This gold-standard approach integrates data from Underwater Weighing (Body Density), Dual-Energy X-ray Absorptiometry (DEXA, for Bone Mineral Content), and Bioelectrical Impedance Spectroscopy (BIS, for Total Body Water) to provide a precise estimation of muscle mass. Results will be reported in kilograms (kg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Body Composition Parameters | Baseline, End of Intervention (up to 24 weeks), and at 6 months post-intervention | Assessment of changes in Fat Mass (FM), Fat-Free Mass (FFM), Total Body Protein (TBPro), Total Body Water (TBW), Intracellular Water (ICW), Extracellular Water (ECW), and hydration of FFM, utilizing the 4- and 5- Compartment models. Assessment of changes in body composition utilizing the 4- and 5-Compartment models. The parameters evaluated include Fat-Free Mass (FFM) and Total Body Protein (TBPro), which will be reported in kilograms (kg). Fat Mass (FM) will be reported both in kilograms (kg) and as a Body Fat Percentage (%). Total Body Water (TBW), Intracellular Water (ICW), and Extracellular Water (ECW) will be reported in liters (L) and as a percentage (%). The hydration of FFM will be reported as a percentage (%). |
| Change from Baseline in Biochemical and Urinary Markers | Baseline, End of Intervention (up to 24 weeks), and at 6 months post-intervention | Assessment of changes in systemic biomarkers. Blood markers include glycemic control (Fasting Glucose, Insulin \[reported in mg/dL or μU/mL\], HbA1c \[%\]), lipid profile (Total, HDL, LDL Cholesterol, Triglycerides \[mg/dL\]), renal/hepatic function (Creatinine, Urea, Bilirubin \[mg/dL\], ALT \[U/L\]), thyroid function (TSH \[mIU/L\]), inflammatory markers (CRP \[mg/L\]), and micronutrient status (B12, Vit D3, Folic Acid, Calcium, Magnesium \[reported in standard clinical units, e.g., pg/mL, ng/mL, mg/dL\]). Urinary biomarkers (Urinary Urea Nitrogen, Albumin, Creatinine) will also be assessed and reported in standard units (e.g., mg/dL, g/24h). |
| Long-term Weight Maintenance Efficiency | From End of Intervention (up to 24 weeks) to 6 months post-intervention | Evaluation of the sustainability of the intervention results after treatment cessation. This measure primarily tracks the change in Body Weight to assess potential weight regain during the follow-up phase. The preservation of Muscle Mass (MM) and Fat Mass (FM) will also be monitored. Changes in Body Weight, MM, and FM will be reported in kilograms (kg) and as a percentage (%) of the weight/mass lost during the active intervention phase. |
| Change from Baseline in Sarcopenia Risk | Baseline, End of Intervention (up to 24 weeks), and at 6 months post-intervention | Participants will be classified as "at risk" for early sarcopenia if they meet at least one of the following criteria: 1. SARC-F score ≥4 (on a scale of 0-10) 2. Handgrip strength below the EWGSOP2 thresholds (men \<27 kg, women \<16 kg) Evaluation of sarcopenia risk using a combination of the Greek validated SARC-F questionnaire and handgrip strength measured via a calibrated dynamometer. The SARC-F score ranges from 0 to 10, where higher scores indicate a greater risk of sarcopenia (worse outcome). Handgrip strength will be reported in kilograms (kg). Participants will be classified as "at risk" for early sarcopenia based on the EWGSOP2 criteria if they meet at least one of the following: 1. SARC-F score ≥ 4, or 2. Handgrip strength below the gender-specific thresholds (men \< 27 kg, women \< 16 kg). The overall outcome will be reported as the change in the continuous parameters (SARC-F score and grip strength in kg) and the proportion (%) of participants classified as "at risk". |
| Change from Baseline in Energy and Macronutrient Intake | Baseline, End of Intervention (up to 24 weeks), and at 6 months post-intervention | Assessment of total energy intake and macronutrient distribution to evaluate dietary adherence. Data will be collected via three-day 24-hour dietary recalls (two weekdays and one weekend day). Total energy intake will be reported in kilocalories (kcal). Macronutrient distribution (specifically protein, carbohydrates, and fats) will be reported in absolute amounts (grams, g) and as a relative proportion of the diet (percentage, %, of total energy intake). |
Countries
Greece
Contacts
CONTACTIoanna Charalampidou
CONTACTChristopher Papandreou
PRINCIPAL_INVESTIGATORChristopher Papandreou
Hellenic Mediterranean University
Outcome results
None listed