---
type: entity
entity_type: research_program
name: MOST-ABLE Trial
full_name: Oral Semaglutide for Parkinson's Disease Motor Symptoms Trial
domain: health
status: active
---

# MOST-ABLE Trial

**Type:** Phase 2/3 randomized controlled trial  
**Intervention:** Oral semaglutide 7mg and 14mg daily  
**Population:** n=99 patients with Parkinson's disease  
**Location:** Japan  
**Primary Endpoint:** Motor symptom improvement (MDS-UPDRS Part III)  

## Overview

MOST-ABLE is the first randomized controlled trial testing semaglutide specifically for Parkinson's disease motor symptoms. Unlike prior GLP-1 Parkinson's trials (exenatide, liraglutide, lixisenatide), this study uses oral semaglutide, which has a distinct CNS access mechanism via tanycytes targeting hypothalamus and brainstem regions.

## Significance

The trial addresses a critical evidence gap: all prior GLP-1 Parkinson's RCTs used older GLP-1 agonists with different CNS penetrance profiles. Exenatide's Phase 3 failure (Lancet Feb 2025) revealed that blood-brain barrier crossing does not guarantee substantia nigra penetrance. Semaglutide's tanycyte-mediated CNS access may provide superior regional distribution, but this remains empirically unproven.

## Timeline

- **2024** — Protocol published, enrollment completed
- **Nov-Dec 2025** — Data collection completed
- **2026** — Results expected (as of May 2026, publication pending)

## Context

Meta-analysis of 5 prior GLP-1 Parkinson's RCTs (n=708) shows narrow motor benefit (MDS-UPDRS Part III -2.06, 95% CI -4.09 to -0.03) but no functional quality of life improvement. MOST-ABLE results will determine whether semaglutide's distinct CNS access mechanism translates to superior clinical efficacy.

## Sources

- PMC12374370 meta-analysis (Jan 2025)
- Session 40 GLP-1 Parkinson's divergence analysis (May 2026)