Apraglutide

Overview

Apraglutide is designed to deliver sustained GLP-2 receptor stimulation with far less frequent dosing than teduglutide. Four amino-acid substitutions relative to native GLP-2 provide DPP-4 resistance, and high plasma-protein binding lowers clearance, extending the elimination half-life to roughly 72 hours—enough for a once-weekly regimen.

A placebo-controlled phase 2 crossover trial in adults with short bowel syndrome and intestinal failure found that once-weekly apraglutide significantly increased urine output, a marker of improved intestinal fluid absorption, and was well tolerated at both 5 mg and 10 mg doses. It subsequently advanced into the phase 3 STARS program in SBS-IF, where it became the first once-weekly GLP-2 analog to show efficacy in reducing parenteral-support needs.

As an intestinotrophic agent, its safety considerations parallel the GLP-2 class, including monitoring for colorectal polyps and gastrointestinal or fluid-balance effects.

Mechanism of Action

Like teduglutide, apraglutide acts through GLP-2 receptors expressed on subepithelial myofibroblasts and enteroendocrine cells rather than directly on enterocytes, promoting epithelial proliferation via mediators such as IGF-1. Its engineered pharmacokinetics aim to provide more constant receptor exposure across a weekly interval, which may improve absorptive outcomes and adherence compared with daily GLP-2 therapy.