Efficacy of GLP-1 Receptor Agonists in Treating Upper and Lower Extremity Lymphedema

Research Protocol: GLP-1Ras - Investigator-Initiated Study

Principal Investigator: Joseph Dayan, MD, MBA

Title: Efficacy of GLP-1 Receptor Agonists in Treating Upper and Lower Extremity Lymphedema

Background and Rationale

Introduction: Lymphedema is an incurable and relentless progressive disease marked by swelling of the upper or lower limb requiring life-long compression. Patients have a high risk of cellulitis and deteriorating quality of life. Lymphedema is a major public health problem with an estimated incidence in the United States of 5 million. There is no cure and no drug to treat this disease.

Literature Review: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now ubiquitous in the United States given their effectiveness in treating obesity and diabetes. Elevated BMI and insulin resistance have been widely reported to worsen lymphedema. Consequently, GLP-1 RAs may have a positive effect on lymphedema. Anecdotally we have observed patients with chronic lymphedema dramatically improve after taking GLP-1 receptor agonists but there is currently no prospective data available.

Rationale: Lymphedema affects millions and currently lacks effective drug treatments, relying mainly on compression therapy. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown potential in managing obesity and diabetes, which can worsen lymphedema. Although anecdotal evidence suggests benefits of GLP-1 RAs for lymphedema patients, rigorous prospective studies are lacking. This study aims to evaluate the effectiveness of GLP-1 RAs in improving quality of life and clinical outcomes in lymphedema patients, thereby addressing a critical gap in literature and potentially offering a new treatment option.

Objectives

Primary Objective: To evaluate the quality-of-life improvements following GLP-1 RA treatment, utilizing the Lymphedema Life Impact Scale (LLIS) as a measurement tool.

Secondary Objectives: To evaluate the efficacy of GLP-1 RAs in reducing limb volume, bioimpedance, compression use, and incidence of cellulitis.

Hypotheses

GLP-1 receptor agonists will improve quality of life and reduce limb volume in lymphedema patients.

Study Design

Type of Study: Prospective, Single arm study, off-label use of GLP-1 receptor agonists to treat upper or lower extremity lymphedema.

Duration: 24 Months

Study Setting: Conduct at an outpatient lymphedema clinic

Population: Adults with Upper and lower extremity Lymphedema, (ISL) stages II and II

Sample Size: 110 participants

Follow-up Visits: Baseline, 3 months, and 6 months post-treatment visit

Participants

Eligibility Criteria

Inclusion Criteria:

Adults 18 years or older with unilateral upper or lower extremity lymphedema Limb volume \> 5% BMI =\> 23 Oncology clearance if there is a cancer history

Exclusion Criteria:

Moderate to severe venous insufficiency Actively using GLP-1 RAs Known intolerance or adverse effect to GLP-1 RAs Medical history or morbidity where GLP-1 RAs are contraindicated as per patient's primary care provider such as MEN syndrome or history of thyroid cancer

Methods

Data Collection:

Lymphedema Life Impact Scale score (validated patient-reported outcome metric) Limb volume Bioimpedance BMI Compression use Incidence of cellulitis

Interventions: GLP-1 RA treatment will be administered by the patient's primary provider for 6 months.

Outcome Measures

Primary Outcome:

Patient reported quality of life outcome (Lymphedema Life Impact Scale)

Secondary Outcomes:

Limb volume Bioimpedance BMI Incidence of cellulitis Compression use

Data Analysis Plan

Statistical Methods:

Utilize appropriate statistical tests, including a t-test with an effect size of 0.15 and a power of 0.95.

To adequately power this study, 74 participants are needed to complete a 6-month course of GLP-1 RA treatment and follow-up. Assuming a dropout rate of 30%, we plan to enroll 110 patients to meet this goal.

Software:

IBM SPSS for data analysis.

• Physiological improvement [Time frame: 6 months]