Peptides Similar to Glepaglutide
Compare Glepaglutide with related peptides and alternatives
📌TL;DR
- •1 similar peptides identified
- •Teduglutide: High - Both are GLP-2 receptor agonists for short bowel syndrome with intestinal failure. Both reduce parenteral support requirements and promote intestinal adaptation through the same receptor pathway.
Quick Comparison
| Peptide | Similarity | Key Differences |
|---|---|---|
| Glepaglutide (current) | - | - |
| Teduglutide | High - Both are GLP-2 receptor agonists for short bowel syndrome with intestinal failure. Both reduce parenteral support requirements and promote intestinal adaptation through the same receptor pathway. | Teduglutide is approved (daily dosing, lyophilized powder requiring reconstitution); glepaglutide is investigational (twice-weekly dosing, ready-to-use autoinjector). Teduglutide requires 50% dose reduction in renal impairment; glepaglutide does not. |
Peptides Related to Glepaglutide#
Glepaglutide is one of three GLP-2 receptor agonists in clinical development for short bowel syndrome. All share the same fundamental mechanism -- GLP-2R activation promoting intestinal adaptation -- but differ in their pharmacokinetic profiles, dosing schedules, and formulations.
Teduglutide (Gattex/Revestive)#
Teduglutide is the only FDA-approved GLP-2 analog (approved 2012) and the most direct comparator to glepaglutide. It is a 33-amino acid GLP-2 analog with a single amino acid substitution (Gly2) that confers DPP-IV resistance.
Mechanism comparison: Both activate the GLP-2 receptor and promote intestinal adaptation through identical downstream pathways (increased villus height, crypt depth, mesenteric blood flow). The therapeutic effects are mechanistically equivalent.
Clinical positioning: Teduglutide is the established standard of care for SBS-IF patients who are candidates for GLP-2 therapy. Glepaglutide is positioned as a next-generation alternative with improved convenience.
| Parameter | Glepaglutide | Teduglutide |
|---|---|---|
| Class | Long-acting GLP-2 analog | GLP-2 analog |
| Length | 39 amino acids | 33 amino acids |
| Modifications | 9 substitutions + hexalysine tail | Single Gly2 substitution |
| Half-life | ~88 hours | ~2 hours |
| Dosing | 10 mg SC twice weekly | 0.05 mg/kg SC daily |
| Formulation | Ready-to-use autoinjector | Lyophilized powder (reconstitution) |
| Renal impairment | No dose adjustment | 50% dose reduction |
| Annual injections | ~104 | ~365 |
| Regulatory status | Phase 3 (FDA CRL) | FDA-approved (2012) |
| Pediatric data | None | Approved for pediatric SBS |
| PS volume reduction | -5.13 L/week (Ph3) | ~4.4 L/week (STEPS, cross-trial) |
Apraglutide#
Apraglutide is another investigational long-acting GLP-2 analog in phase 3 development, using fatty acid conjugation to achieve once-weekly dosing. It is being developed by VectivBio (now part of Alexion/AstraZeneca).
Key differences: Apraglutide achieves its extended action through a fatty acid modification (similar in concept to semaglutide for GLP-1), whereas glepaglutide uses amino acid substitutions and a SIP tail. Apraglutide is dosed once weekly; glepaglutide requires twice-weekly dosing. Apraglutide requires reconstitution from lyophilized powder.
| Parameter | Glepaglutide | Apraglutide |
|---|---|---|
| Modification strategy | Amino acid substitutions + SIP tail | Fatty acid conjugation |
| Half-life | ~88 hours | ~30 hours |
| Dosing | Twice weekly | Once weekly |
| Formulation | Ready-to-use liquid | Lyophilized powder |
| Phase 3 status | CRL (additional trial planned) | Ongoing |
| Developer | Zealand Pharma | VectivBio/Alexion |
Native GLP-2#
Native human GLP-2 is the 33-amino acid endogenous hormone secreted by intestinal L-cells. It has a half-life of approximately 7 minutes and is not suitable for therapeutic use. All three analogs are designed to reproduce its intestinotrophic effects with clinically practical pharmacokinetics.
Summary Comparison#
| Feature | Glepaglutide | Teduglutide | Apraglutide |
|---|---|---|---|
| Mechanism | GLP-2R agonist | GLP-2R agonist | GLP-2R agonist |
| Primary indication | SBS-IF | SBS-IF | SBS-IF |
| Dosing frequency | Twice weekly | Daily | Once weekly |
| Formulation | Ready-to-use liquid | Lyophilized | Lyophilized |
| Reconstitution | No | Yes (daily) | Yes |
| Renal dose adjustment | No | Yes | TBD |
| Key AEs | GI events, ISRs | GI events, ISRs, polyps | GI events, ISRs |
| Regulatory status | Phase 3 (CRL) | Approved | Phase 3 |
| Pediatric indication | None | Approved | None |
Related Reading#
Frequently Asked Questions About Glepaglutide
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