Apraglutide
A next-generation, long-acting glucagon-like peptide-2 (GLP-2) analog engineered for once-weekly dosing in short bowel syndrome.
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.
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References (1)
- [1]Eliasson J, Hvistendahl MK, Freund N, et al. Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial JPEN Journal of Parenteral and Enteral Nutrition (2022)
→ Once-weekly apraglutide significantly increased intestinal fluid absorption (urine output) in short bowel syndrome with intestinal failure and was well tolerated.
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