Effect of GLP-1 Receptor Agonists on Body Composition in Obesity: The Role of Dietary Protein Consumption in Muscle Mass Maintenance (LEAN-PRO GLP-1)

Hellenic Mediterranean University

Status: Enrolling

Conditions: Obesity

Treatments: Behavioral: Control (Standard Mediterranean Diet Counseling); Behavioral: High Protein Dietary Intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT07495904

159302

Protocol No. 44248 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 estimated patients

Sex: All

Ages: 30 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

GLP-1 + Standard Diet

Active Comparator group

Description:

Participants will receive GLP-1 treatment alongside standard nutritional counseling based on the Mediterranean diet pattern, provided within the framework of usual clinical practice.

Treatment:

Behavioral: Control (Standard Mediterranean Diet Counseling)

GLP-1 + High Protein Diet

Experimental group

Description:

Participants will receive GLP-1 treatment along with a specialized dietary intervention featuring individualized guidelines aimed at increasing daily protein intake.

Treatment:

Behavioral: High Protein Dietary Intervention