--- title: "Glepaglutide | PepTracker Pro" url: https://peptrackerpro.com/peptides/glepaglutide description: "A long-acting glucagon-like peptide-2 (GLP-2) analog given by once- or twice-weekly subcutaneous injection that helps the gut absorb more nutrients in short bowel syndrome, reducing dependence on IV (parenteral) nutrition." lang: en --- Skip to main content **Educational information only.** This site does not provide medical advice. Read full disclaimer (https://peptrackerpro.com/disclaimer) **Research-only content.** This page is for educational purposes and does not constitute medical advice. Read full disclaimer → (https://peptrackerpro.com/research-disclaimer) # Glepaglutide Medium Evidence A long-acting glucagon-like peptide-2 (GLP-2) analog given by once- or twice-weekly subcutaneous injection that helps the gut absorb more nutrients in short bowel syndrome, reducing dependence on IV (parenteral) nutrition. Aliases ZP1848 +3 more Evidence Medium Evidence Last Updated 2026-07-19 Reading Time 4 min ## What It Is Glepaglutide (ZP1848), developed by Zealand Pharma, is a long-acting analog of glucagon-like peptide-2 (GLP-2), a hormone the intestine releases after eating that promotes growth and absorptive capacity of the gut lining. Unlike the GLP-1 and GIP peptides that dominate the obesity and diabetes conversation, glepaglutide is an intestinotrophic (gut-growing) peptide developed for short bowel syndrome with intestinal failure (SBS-IF) — a rare, serious condition in which people who have lost much of their small intestine cannot absorb enough nutrition and depend on parenteral support (intravenous nutrition and fluids). Glepaglutide is engineered for stability in a ready-to-use aqueous (liquid) formulation delivered by autoinjector, with a long effective half-life of roughly 88 hours that allows once- or twice-weekly dosing rather than the daily injection required by the first approved GLP-2 analog, teduglutide (Gattex/Revestive). It works as a GLP-2 receptor agonist: by activating GLP-2 receptors in the gut it increases intestinal mucosal mass, villus height and blood flow, improving the remaining bowel's ability to absorb fluid and nutrients. In the pivotal Phase 3 EASE-SBS 1 trial (106 patients), 10 mg twice weekly significantly reduced weekly parenteral support volume versus placebo (mean change −5.13 vs −2.85 L/week; P=0.0039), about two-thirds of twice-weekly patients achieved a clinically meaningful (>20%) reduction in IV support, and nine glepaglutide-treated patients were fully weaned off parenteral support versus none on placebo. In December 2024 the U.S. FDA issued a Complete Response Letter requesting an additional trial; Zealand Pharma submitted a European Marketing Authorization Application to the EMA in June 2025 (supported by EASE-1 and the EASE-2/EASE-3 long-term extensions) and planned a new confirmatory Phase 3 for U.S. approval. Glepaglutide is an investigational prescription peptide for a specific disease — not an approved or self-administered wellness 'research peptide.' Also known as: ZP1848, glepaglutide acetate, long-acting GLP-2 analog, GLP-2 analogue ## Regulatory Status Investigational — not approved in the U.S.; EU marketing application under review Glepaglutide (ZP1848, Zealand Pharma) is an investigational long-acting GLP-2 analog for short bowel syndrome with intestinal failure. The U.S. FDA issued a Complete Response Letter on December 19, 2024, concluding the application did not provide substantial evidence of efficacy/safety for the proposed dose and requesting an additional clinical trial. Zealand Pharma submitted a Marketing Authorization Application to the European Medicines Agency (EMA) in June 2025 based on the Phase 3 EASE-SBS 1 trial and the EASE-2/EASE-3 extensions, and planned a further Phase 3 trial to support U.S. approval. It is not approved or marketed and is administered by prescription under specialist care. Effective: June 2026 View FDA Source (https://www.globenewswire.com/news-release/2024/12/19/3000220/0/en/U-S-Food-and-Drug-Administration-issues-Complete-Response-Letter-for-the-glepaglutide-New-Drug-Application-for-the-treatment-of-short-bowel-syndrome.html) ## Why Researchers Study It Glepaglutide is studied because short bowel syndrome with intestinal failure is a rare but devastating condition in which patients depend on lengthy daily IV nutrition, with major impacts on quality of life and risk of line infections and liver complications. GLP-2 directly drives growth and absorptive capacity of the remaining intestine, so a long-acting GLP-2 analog that can be dosed once or twice weekly — rather than the daily subcutaneous injection of teduglutide — could meaningfully reduce treatment burden while cutting or eliminating parenteral support. Researchers are interested in glepaglutide's ready-to-use liquid autoinjector formulation, its ~88-hour effective half-life, its ability to wean some patients off IV nutrition entirely, and how it compares with other GLP-2 analogs (teduglutide and the once-weekly apraglutide) in the emerging class of intestinotrophic peptides. ## Proposed Mechanisms - Acts as a GLP-2 receptor agonist, mimicking the natural intestinal hormone glucagon-like peptide-2 (GLP-2) - Stimulates growth of the intestinal mucosa — increasing villus height, crypt depth and absorptive surface area of the remaining bowel - Increases intestinal and mesenteric blood flow, supporting nutrient and fluid uptake - Slows gastric emptying and reduces intestinal secretion, improving the time and capacity for absorption - Improves fluid and energy absorption, lowering the volume of parenteral (IV) nutrition and fluids patients require - Engineered for a long effective half-life (~88 hours) in a stable aqueous formulation, enabling once- or twice-weekly subcutaneous dosing ## Evidence Snapshot Medium Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Clinical (Phase 3, EASE-SBS 1) | 106 adults with short bowel syndrome and intestinal failure dependent on parenteral support, randomized to glepaglutide 10 mg once weekly, twice weekly, or placebo for 24 weeks | Positive (twice weekly): significant reduction in weekly parenteral support volume vs placebo (mean change −5.13 vs −2.85 L/week; P=0.0039); ~66% achieved >20% reduction and 9 patients weaned off parenteral support. Once-weekly dosing showed a numeric but non-significant reduction. | Source: https://www.gastrojournal.org/article/S0016-5085(24)05787-1/fulltext | | Clinical (Phase 3 long-term extensions, EASE-2 / EASE-3) | Ongoing open-label long-term safety and durability extensions of EASE-SBS 1 | Supportive: interim results used alongside EASE-1 to support the EU Marketing Authorization Application (submitted June 2025) | Source: https://www.globenewswire.com/news-release/2025/06/02/3091534/0/en/Zealand-Pharma-submits-Marketing-Authorization-Application-to-the-European-Medicines-Agency-for-glepaglutide-in-short-bowel-syndrome.html | | Regulatory (U.S. FDA) | New Drug Application review for SBS with intestinal failure | Complete Response Letter (Dec 19, 2024): FDA found insufficient substantial evidence for the to-be-marketed dose and requested an additional clinical trial | Source: https://www.biospace.com/press-releases/u-s-food-and-drug-administration-issues-complete-response-letter-for-the-glepaglutide-new-drug-application-for-the-treatment-of-short-bowel-syndrome | | Clinical pharmacology (Phase 1) | Pharmacokinetics characterizing the long ~88-hour effective half-life supporting weekly dosing | Supportive: long-acting PK profile consistent with once-/twice-weekly subcutaneous administration | Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC9545924/ | ## Commonly Discussed Benefits Gut Health: https://peptrackerpro.com/benefits/gut-health Researching Glepaglutide? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=glepaglutide) ## Safety & Cautions - An investigational, unapproved peptide — the U.S. FDA has not approved it and requested an additional trial; it is not available outside clinical development and the EU review is ongoing - Intended only for short bowel syndrome with intestinal failure under specialist (gastroenterology/nutrition) care — not a general wellness or self-experimentation peptide - GLP-2 analogs are intestinotrophic (they stimulate cell growth), so they require monitoring for intestinal polyps/neoplasia and carry class warnings; colonoscopy and surveillance are part of GLP-2 treatment - Reported GLP-2-class side effects include gastrointestinal symptoms (abdominal pain, swelling/stoma changes), fluid overload, and potential gallbladder, biliary and pancreatic effects requiring monitoring - Dosing, long-term safety and the to-be-marketed regimen are still being confirmed in additional trials - Any antimicrobial or 'gut-healing' claims sold by unregulated 'research peptide' vendors are unsupported — legitimate use is by prescription within approved indications or clinical trials ## Comparisons See how Glepaglutide compares to related peptides: Glepaglutide vs Apraglutide: https://peptrackerpro.com/compare/glepaglutide-vs-apraglutide Glepaglutide vs Dapiglutide: https://peptrackerpro.com/compare/glepaglutide-vs-dapiglutide Glepaglutide vs Larazotide: https://peptrackerpro.com/compare/glepaglutide-vs-larazotide Glepaglutide vs Palopegteriparatide: https://peptrackerpro.com/compare/glepaglutide-vs-palopegteriparatide Glepaglutide vs Semaglutide: https://peptrackerpro.com/compare/glepaglutide-vs-semaglutide Glepaglutide vs Survodutide: https://peptrackerpro.com/compare/glepaglutide-vs-survodutide Glepaglutide vs Tirzepatide: https://peptrackerpro.com/compare/glepaglutide-vs-tirzepatide ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] U.S. FDA issues Complete Response Letter for the glepaglutide NDA for short bowel syndrome — Zealand Pharma (Dec 19, 2024) PubMed (https://www.globenewswire.com/news-release/2024/12/19/3000220/0/en/U-S-Food-and-Drug-Administration-issues-Complete-Response-Letter-for-the-glepaglutide-New-Drug-Application-for-the-treatment-of-short-bowel-syndrome.html) 2. [2] Glepaglutide, a Long-Acting GLP-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 RCT (EASE-SBS 1) — Gastroenterology PubMed (https://www.gastrojournal.org/article/S0016-5085(24)05787-1/fulltext) 3. [3] Zealand Pharma submits Marketing Authorization Application to the EMA for glepaglutide in short bowel syndrome (June 2025) PubMed (https://www.globenewswire.com/news-release/2025/06/02/3091534/0/en/Zealand-Pharma-submits-Marketing-Authorization-Application-to-the-European-Medicines-Agency-for-glepaglutide-in-short-bowel-syndrome.html) 4. [4] Apraglutide / GLP-2 analog once-weekly metabolic balance trial in SBS — PMC (class context) PubMed (https://pmc.ncbi.nlm.nih.gov/articles/PMC9545924/) 5. [5] FDA Issues Complete Response Letter for Much-Anticipated GLP-2 Analog — Pharmacy Times PubMed (https://www.pharmacytimes.com/view/fda-issues-complete-response-letter-for-much-anticipated-glp-2-analog) ### Keep researching in the app - Log Glepaglutide to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack Open PepTracker Pro Free: https://app.peptrackerpro.com/?add=glepaglutide Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### Apraglutide Medium Evidence A long-acting, once-weekly glucagon-like peptide-2 (GLP-2) analog that boosts intestinal absorption in short bowel syndrome, aiming to reduce dependence on IV (parenteral) nutrition; in Phase 3 development with a confirmatory trial required by the FDA. View Details: https://peptrackerpro.com/peptides/apraglutide \+ Compare: https://peptrackerpro.com/compare?select=apraglutide Track in App: https://app.peptrackerpro.com/?add=apraglutide ### Dapiglutide Medium Evidence A long-acting, once-weekly dual GLP-1 and GLP-2 receptor agonist peptide (Zealand Pharma) developed for obesity, uniquely pairing GLP-1-driven weight loss with GLP-2 activation intended to improve intestinal barrier function and reduce obesity-related low-grade inflammation; development was paused in November 2025. Weight Management: https://peptrackerpro.com/benefits/weight-management Metabolism: https://peptrackerpro.com/benefits/metabolism Gut Health: https://peptrackerpro.com/benefits/gut-health Inflammation: https://peptrackerpro.com/benefits/inflammation View Details: https://peptrackerpro.com/peptides/dapiglutide \+ Compare: https://peptrackerpro.com/compare?select=dapiglutide Track in App: https://app.peptrackerpro.com/?add=dapiglutide ### Larazotide Medium Evidence A synthetic peptide tight junction regulator in clinical trials for celiac disease, designed to prevent intestinal permeability caused by gluten exposure. Gut Health: https://peptrackerpro.com/benefits/gut-health Inflammation: https://peptrackerpro.com/benefits/inflammation Immune Support: https://peptrackerpro.com/benefits/immune-support View Details: https://peptrackerpro.com/peptides/larazotide \+ Compare: https://peptrackerpro.com/compare?select=larazotide Track in App: https://app.peptrackerpro.com/?add=larazotide ### Palopegteriparatide High Evidence Palopegteriparatide (Yorvipath, developed as TransCon PTH) is Ascendis Pharma's once-daily prodrug of parathyroid hormone (1-34). An inert methoxy-PEG carrier is attached to PTH(1-34) through a TransCon linker that auto-cleaves at physiologic pH and temperature, releasing unmodified native-sequence PTH slowly enough to hold hormone levels inside the physiologic range for a full 24 hours. It is the first therapy approved as a true hormone replacement for chronic hypoparathyroidism rather than as an add-on to calcium and active vitamin D: in the Phase 3 PaTHway trial 78.7% of treated adults met a composite endpoint of normal serum calcium plus independence from conventional therapy at week 26, versus 4.8% on placebo. The FDA approved Yorvipath on August 9, 2024. Rare Disease Treatment (https://peptrackerpro.com/benefits/rare-disease-treatment)Hormone Support (https://peptrackerpro.com/benefits/hormone-support)Bone Growth (https://peptrackerpro.com/benefits/bone-growth)Disease Modification (https://peptrackerpro.com/benefits/disease-modification)+1 more View Details: https://peptrackerpro.com/peptides/palopegteriparatide \+ Compare: https://peptrackerpro.com/compare?select=palopegteriparatide Track in App: https://app.peptrackerpro.com/?add=palopegteriparatide ### Semaglutide High Evidence A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management. Weight Management (https://peptrackerpro.com/benefits/weight-management)Appetite Regulation (https://peptrackerpro.com/benefits/appetite-regulation)Metabolism (https://peptrackerpro.com/benefits/metabolism)Fat Loss (https://peptrackerpro.com/benefits/fat-loss)+3 more View Details: https://peptrackerpro.com/peptides/semaglutide \+ Compare: https://peptrackerpro.com/compare?select=semaglutide Track in App: https://app.peptrackerpro.com/?add=semaglutide ### Survodutide Medium Evidence A dual GLP-1/glucagon receptor agonist with FDA Breakthrough Therapy designation for MASH and Priority Review NDA filed February 2026. Phase 3 SYNCHRONIZE-1 reported 16.6% weight loss at 76 weeks; approval possible Q3 2026. Weight Management: https://peptrackerpro.com/benefits/weight-management Appetite Regulation: https://peptrackerpro.com/benefits/appetite-regulation Metabolism: https://peptrackerpro.com/benefits/metabolism Fat Loss: https://peptrackerpro.com/benefits/fat-loss View Details: https://peptrackerpro.com/peptides/survodutide \+ Compare: https://peptrackerpro.com/compare?select=survodutide Track in App: https://app.peptrackerpro.com/?add=survodutide ### Tirzepatide High Evidence A dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes, weight management, and MASH with liver fibrosis. Weight Management (https://peptrackerpro.com/benefits/weight-management)Appetite Regulation (https://peptrackerpro.com/benefits/appetite-regulation)Metabolism (https://peptrackerpro.com/benefits/metabolism)Fat Loss (https://peptrackerpro.com/benefits/fat-loss)+1 more View Details: https://peptrackerpro.com/peptides/tirzepatide \+ Compare: https://peptrackerpro.com/compare?select=tirzepatide Track in App: https://app.peptrackerpro.com/?add=tirzepatide ## Structured data ```json [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Glepaglutide", "description": "A long-acting glucagon-like peptide-2 (GLP-2) analog given by once- or twice-weekly subcutaneous injection that helps the gut absorb more nutrients in short bowel syndrome, reducing dependence on IV (parenteral) nutrition.", "url": "https://peptrackerpro.com/peptides/glepaglutide", "lastReviewed": "2026-07-19", "reviewedBy": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "isPartOf": { "@type": "WebSite", "name": "PepTracker Pro", "url": "https://peptrackerpro.com" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Peptides", "item": "https://peptrackerpro.com/peptides" }, { "@type": "ListItem", "position": 3, "name": "Glepaglutide", "item": "https://peptrackerpro.com/peptides/glepaglutide" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "Patients, caregivers and clinicians dealing with short bowel syndrome and intestinal failure who depend on parenteral (IV) nutrition?", "acceptedAnswer": { "@type": "Answer", "text": "Glepaglutide is a research peptide studied in preclinical models. 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