EFFICACY AND MARKET SHARE OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS FOR CURRENT OFF-LABEL USES: A TARGETED LITERATURE REVIEW
Author(s)
Rachel Gamburg, BSc1, Vishnu Bharadwaj Suresh, MSc2, Ruihong Wang, MSc1, Coby Martin, MSc3;
1Axtria Inc, Boston, MA, USA, 2Axtria Inc, Berkeley Heights, NJ, USA, 3Axtria Inc, Toronto, ON, Canada
1Axtria Inc, Boston, MA, USA, 2Axtria Inc, Berkeley Heights, NJ, USA, 3Axtria Inc, Toronto, ON, Canada
OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs or simply GLP-1s) are increasingly used in the United States for off-label indications, garnering attention from optimistic patients and providers, as well as skeptical researchers. However, the prescription rate for each indication is not well known, nor is the efficacy or cost-effectiveness. Therefore, we reviewed literature to better understand for off-label use, focusing on alcohol and drug addiction, food addiction, osteoarthritis, Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and polycystic ovary syndrome (PCOS).
METHODS: We conducted a brief systematic literature review using PubMed and Embase databases. Relevant studies were identified using search terms related to GLP-1 RAs, off-label indications, efficacy, cost-effectiveness, and off-label prescription.
RESULTS: We identified 396 articles through database searches. Among these, new indications were typically investigated alongside comorbid approved indications. Several evaluating efficacy have shown promising results. In knee osteoarthritis with obesity, semaglutide had significantly greater reductions in body weight (-13.7% vs -3.2%) and pain (-41.7 vs -27.5 points) than placebo. AD and PD also show promise, with pooled analyses demonstrating improvements in cognitive function in AD (mean difference = 2.16) and modest improvements in motor symptoms in PD, including reductions in MDS-UPDRS part III scores of up to −2.5 points compared with placebo. Although, negative trial results have recently surfaced. In PCOS, GLP-1-based combination therapy significantly improved insulin resistance (HOMA-IR = −0.9) and reduced BMI (mean difference = −0.4). Estimates of off-label GLP-1 prescription rates are high, with one study finding a median rate of 37.7%.
CONCLUSIONS: GLP-1 RAs are expanding to treat several indications. Efficacy is evident in some off-label indications, but risks, especially long term, remain uncertain. As a result of high off-label use, market share of GLP-1 RAs varies across communities, necessitating further investigation and intervention as the landscape evolves.
METHODS: We conducted a brief systematic literature review using PubMed and Embase databases. Relevant studies were identified using search terms related to GLP-1 RAs, off-label indications, efficacy, cost-effectiveness, and off-label prescription.
RESULTS: We identified 396 articles through database searches. Among these, new indications were typically investigated alongside comorbid approved indications. Several evaluating efficacy have shown promising results. In knee osteoarthritis with obesity, semaglutide had significantly greater reductions in body weight (-13.7% vs -3.2%) and pain (-41.7 vs -27.5 points) than placebo. AD and PD also show promise, with pooled analyses demonstrating improvements in cognitive function in AD (mean difference = 2.16) and modest improvements in motor symptoms in PD, including reductions in MDS-UPDRS part III scores of up to −2.5 points compared with placebo. Although, negative trial results have recently surfaced. In PCOS, GLP-1-based combination therapy significantly improved insulin resistance (HOMA-IR = −0.9) and reduced BMI (mean difference = −0.4). Estimates of off-label GLP-1 prescription rates are high, with one study finding a median rate of 37.7%.
CONCLUSIONS: GLP-1 RAs are expanding to treat several indications. Efficacy is evident in some off-label indications, but risks, especially long term, remain uncertain. As a result of high off-label use, market share of GLP-1 RAs varies across communities, necessitating further investigation and intervention as the landscape evolves.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
MT2
Topic
Medical Technologies
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Neurological Disorders, SDC: Reproductive & Sexual Health, STA: Multiple/Other Specialized Treatments