MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Glepaglutide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Glepaglutide (ZP1848) is a long-acting GLP-2 receptor agonist designed by Zealand Pharma for short bowel syndrome. By activating intestinal GLP-2 receptors it enlarges the absorptive mucosal surface, increases gut blood flow and slows transit, helping patients absorb more fluid and nutrients and reduce intravenous parenteral support. Its hallmark is a self-assembling subcutaneous depot that stretches the effective half-life to roughly 88 hours, so it is dosed once or twice weekly rather than daily like teduglutide. In the pivotal Phase 3 trial (NCT03690206; PMID 39708985), 10 mg subcutaneously twice weekly cut weekly parenteral support volume by 5.13 L versus 2.85 L on placebo. The compound is investigational: it holds FDA orphan-drug designation but received a Complete Response Letter in December 2024 and is not approved for any indication. The dosing figures here are an educational subcutaneous reconstitution reference, not medical advice.
Reconstitute: Add 1 mL bacteriostatic water → 20 mg/mL concentration.
Typical dose: 10 mg SC once or twice weekly
Easy measuring: At 20 mg/mL, 1 unit = 0.01 mL = 0.2 mg (200 mcg) on a U-100 insulin syringe.
Storage: Lyophilized glepaglutide stored refrigerated at 2-8 °C, protected from light; do not freeze. The reconstituted solution is kept refrigerated at 2-8 °C and used within the validated in-use window (typically a few days). Allow to reach room temperature before injecting.
Half-life: Effective half-life about 88 hours at 10 mg (around 124 hours at 5 mg), driven by slow release of two depot metabolites that comprise >98% of exposure, supporting once- or twice-weekly dosing.
Route: Subcutaneous injection (abdomen or thigh), reconstituted from lyophilized powder. This is the genuine clinical route; in trials a pen/autoinjector is used.
Status: Investigational. FDA orphan-drug designation; Complete Response Letter December 2024; not FDA- or EMA-approved. Research/educational use only.
About Glepaglutide
Glepaglutide (developmental code ZP1848) is a long-acting synthetic analogue of glucagon-like peptide-2 (GLP-2), the intestinotrophic hormone released by intestinal L-cells. It is engineered to resist enzymatic breakdown and to form a slow-release subcutaneous depot, allowing the very infrequent dosing that distinguishes it from the daily GLP-2 analogue teduglutide. Unlike many compounds catalogued on this site, glepaglutide's real-world route genuinely is subcutaneous injection, so the reconstitution figures below map directly onto how it is actually administered [1][3].\n\nThis guide models a 20 mg vial reconstituted with 1.0 mL of bacteriostatic water (20 mg/mL) so that the studied 10 mg dose lands at a clean 50 units (0.5 mL) on a U-100 insulin syringe, with two full doses per vial. In the pivotal Phase 3 program the effective Glepaglutide dosage was 10 mg injected subcutaneously twice weekly; a 10 mg once-weekly regimen was also tested as a lower-frequency option [1].\n\nFrequency: Inject 10 mg subcutaneously twice weekly (the Phase 3 regimen that met its primary endpoint); a once-weekly 10 mg schedule was also studied. Glepaglutide is investigational, it received a U.S. FDA Complete Response Letter in December 2024 and is not approved for any use, so these figures are an educational reference only, not medical advice [9].
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner wall of the 20 mg glepaglutide vial; do not aim the stream directly at the lyophilized powder, and avoid vigorous shaking that could damage the peptide or cause foaming.
Let the vial rest, then gently swirl or roll it until the solution is completely clear, yielding a 20 mg/mL concentration (200 mcg per insulin-syringe unit).
Store the reconstituted solution refrigerated at 2-8 °C, protected from light, and do not freeze; draw 50 units (0.5 mL = 10 mg) per dose and rotate subcutaneous sites on the abdomen or thigh.
Swab the vial septum and the injection site with alcohol before each use; with two 10 mg doses per vial, plan twice-weekly injections and discard any solution past the validated in-use window.
Interactive Glepaglutide Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 1mL water yields 20.00 mg/mL. To evaluate a 250mcg dose, pull to 1.3 units (1 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Initiation — 10 mg once weekly (lower-frequency option) | 10000 mcg (10 mg) | 50 units (0.50 mL) |
| Maintenance — 10 mg twice weekly (Phase 3 effective regimen) | 10000 mcg (10 mg) | 50 units (0.50 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (Glepaglutide, 20 mg each):
- check8 weeks at 10 mg twice weekly (16 injections) ≈ 8 vials (160 mg total; 2 doses per vial)
- check12 weeks at 10 mg twice weekly (24 injections) ≈ 12 vials (240 mg total)
- check16 weeks at 10 mg twice weekly (32 injections) ≈ 16 vials (320 mg total)
- checkA once-weekly 10 mg option halves vial use (e.g., 16 weeks ≈ 8 vials)
Insulin Syringes (U-100):
- checkTwice-weekly dosing: 2 syringes per week
- check8 weeks ≈ 16 syringes; 12 weeks ≈ 24 syringes; 16 weeks ≈ 32 syringes
- checkEach 10 mg dose = 50 units (0.5 mL), comfortably within one syringe
Bacteriostatic Water (30 mL bottles): Use 1.0 mL per 20 mg vial for reconstitution.
- check8 weeks ≈ 8 mL (about 1 bottle)
- check12 weeks ≈ 12 mL (about 1 bottle)
- check16 weeks ≈ 16 mL (about 1 bottle)
Alcohol Swabs:
- check1-2 swabs per injection (vial septum + injection site)
- check8 weeks (16 injections) ≈ 16-32 swabs; 12 weeks (24 injections) ≈ 24-48 swabs
- check16 weeks (32 injections) ≈ 32-64 swabs; keep extras for re-swabbing multi-dose vials
Mechanism of Action (MOA)
Glepaglutide is a synthetic analogue of glucagon-like peptide-2 (GLP-2), a 33-amino-acid hormone co-secreted with GLP-1 by enteroendocrine L-cells of the distal small intestine and colon in response to nutrient intake. Native GLP-2 is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4), giving it a half-life of only minutes. Glepaglutide carries amino-acid modifications that confer DPP-4 resistance and, critically, a sequence that drives reversible self-association into a subcutaneous depot, so the molecule and its two principal metabolites are released slowly into the circulation over days [3].\n\nThe drug acts as an agonist at the GLP-2 receptor (GLP-2R), a G-protein-coupled receptor expressed not on enterocytes directly but on subepithelial myofibroblasts, enteroendocrine cells and enteric neurons. Receptor activation triggers paracrine release of growth factors such as IGF-1, keratinocyte growth factor and nitric oxide. The net intestinotrophic effect is increased crypt-cell proliferation, reduced enterocyte apoptosis, taller villi and a larger mucosal absorptive surface, together with greater mesenteric and intestinal blood flow, slowed gastric emptying and gastric acid secretion, and improved epithelial barrier function [1][5]. In short bowel syndrome, where surgical loss of intestine leaves patients unable to absorb enough fluid and nutrients and dependent on intravenous parenteral support, these adaptations raise wet-weight and energy absorption and let many patients lower, or in some cases wean, parenteral support [1][2].\n\nPharmacokinetics define glepaglutide's main clinical advantage. After a 10 mg subcutaneous dose the parent peptide peaks within about 30 minutes, but slow release of the M1 and M2 metabolites from the subcutaneous depot dominates exposure, accounting for more than 98% of total drug at steady state and giving an estimated effective half-life near 88 hours (about 124 hours at 5 mg) [3]. Steady state is reached by roughly the third weekly injection, with substantial accumulation. This protracted profile is what permits once- or twice-weekly dosing, in contrast to teduglutide, the first approved GLP-2 analogue, which must be injected daily. Exposure rises in renal impairment, a relevant consideration because many SBS patients have compromised kidney function [4].\n\nGlepaglutide is administered subcutaneously, typically via a reconstituted pen/autoinjector in trials, so the injection-based protocol on this page reflects its genuine route. Regulatory status, however, is investigational: the FDA granted orphan-drug designation but issued a Complete Response Letter for the New Drug Application in December 2024, citing insufficient evidence for the to-be-marketed dose, and a European marketing authorization application was submitted in 2025 [9]. Nothing here is medical advice.
Clinical Trial Efficacy Highlights
- starNaimi and colleagues (2019, Lancet Gastroenterology & Hepatology) ran the first-in-patient dose-finding Phase 2 trial: 18 adults with short bowel syndrome received daily subcutaneous glepaglutide at 0.1, 1 or 10 mg for 3 weeks each. The 1 mg and 10 mg doses significantly increased intestinal wet-weight and energy absorption versus baseline, whereas 0.1 mg did not, establishing the active dose range and a favorable tolerability profile [2].
- starIn the pivotal Phase 3 randomized, double-blind, placebo-controlled trial (Jeppesen et al., 2025, Gastroenterology; NCT03690206), 106 patients with SBS and intestinal failure requiring parenteral support at least 3 days/week were randomized 1:1:1 to glepaglutide 10 mg twice weekly, 10 mg once weekly, or placebo for 24 weeks. The twice-weekly arm met the primary endpoint, reducing weekly parenteral support volume by a mean of 5.13 L/week versus 2.85 L/week on placebo (P = .0039) [1].
- starA healthy-subject pharmacokinetic study (Agersnap et al., 2022, Clinical Drug Investigation) gave single 5 mg or 10 mg subcutaneous doses and showed that two slowly released depot metabolites (M1 and M2) accounted for more than 98% of total exposure, producing an estimated effective half-life of roughly 88 hours at 10 mg and 124 hours at 5 mg, the pharmacologic basis for weekly or twice-weekly dosing [3].
- starA mechanistic Phase 2 sub-study (Naimi et al., 2023, JPEN, Journal of Parenteral and Enteral Nutrition) used imaging and biopsy to document that glepaglutide increased villus height, mucosal thickness and intestinal perfusion in SBS patients, providing structural confirmation of the hormone's intestinotrophic action [5].
- starA separate Phase 2 analysis (Naimi et al., 2019, EBioMedicine) evaluated markers of liver status during glepaglutide treatment in SBS patients, addressing the relevant question of hepatobiliary effects in a population prone to intestinal-failure-associated liver disease [6].
- starA dedicated renal-impairment pharmacokinetic, safety and tolerability study (Agersnap et al., 2023, Clinical Pharmacokinetics) found that glepaglutide exposure increased with declining kidney function, informing dose considerations in SBS patients who frequently have compromised renal function [4].
- starRegulatory context: the U.S. FDA granted glepaglutide orphan-drug designation but issued a Complete Response Letter for the New Drug Application in December 2024, concluding the submitted data did not establish substantial evidence of efficacy and safety for the to-be-marketed dose; a European marketing authorization application was filed in 2025, so the compound remains investigational [8][9].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningGastrointestinal effects are the most common: nausea, abdominal pain, abdominal distension and vomiting were each reported in more than 20% of patients in Phase 2, reflecting the trophic and motility actions of GLP-2 on the gut [2].
- warningStoma-related complications occurred more often with active drug, and more frequently at higher dosing frequency (about 41% with twice-weekly vs 25% with once-weekly vs 0% with placebo in the stoma subgroup of the Phase 3 trial); stoma output, edema and bleeding warrant monitoring [1].
- warningFluid handling can shift as absorption improves: peripheral edema, polyuria and fluid overload were observed, requiring parenteral-support volumes to be down-titrated carefully to avoid over- or under-hydration [1][2].
- warningAs a class effect, GLP-2 receptor agonists stimulate intestinal growth, so there is a theoretical risk of accelerating colorectal polyps or neoplasia; the labeling for the approved analogue teduglutide requires baseline and periodic colonoscopy/imaging, a precaution that applies to investigational GLP-2 agonists [5].
- warningGLP-2 agonism is also associated with hepatobiliary and pancreatic events (gallbladder disease, cholecystitis, biliary obstruction and pancreatitis) for the class, alongside a risk of intestinal or stomal obstruction; clinical monitoring of these systems is advised [6].
- warningSerious adverse events in Phase 3 were generally consistent with underlying SBS and comorbidities, but SBS-related serious events in the twice-weekly arm included stoma-site hemorrhage with anemic blood loss, metabolic acidosis (including d-lactic acidosis) and iron-deficiency anemia [1].
- warningGlepaglutide exposure rises in renal impairment, so patients with reduced kidney function may need additional caution and monitoring [4].
- warningRegulatory/research status: glepaglutide is NOT approved by the FDA or EMA. It received an FDA Complete Response Letter in December 2024 and remains investigational; it should be regarded as research/educational only, and long-term safety outside controlled trials is not established [8][9].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Glepaglutide dosage?expand_more
The most-studied Glepaglutide dosage is 10 mg injected subcutaneously twice weekly, the regimen that met the primary endpoint in the Phase 3 short bowel syndrome trial (reducing weekly parenteral support volume by 5.13 L vs 2.85 L on placebo). A 10 mg once-weekly schedule was also evaluated as a lower-frequency option. On the educational model used here (20 mg vial reconstituted with 1.0 mL of bacteriostatic water, giving 20 mg/mL), each 10 mg dose is 50 units (0.5 mL) on a U-100 insulin syringe, with two doses per vial.
Is Glepaglutide FDA approved?expand_more
No. Glepaglutide is investigational and not approved by the FDA or EMA for any indication. It holds FDA orphan-drug designation for short bowel syndrome, but in December 2024 the FDA issued a Complete Response Letter for the New Drug Application, concluding the data did not establish substantial evidence for the to-be-marketed dose. Zealand Pharma submitted a European marketing authorization application in 2025. Everything on this page is educational, not a prescription or medical advice.
What is the Glepaglutide half life?expand_more
Glepaglutide has an unusually long effective half-life because it forms a slow-release subcutaneous depot. In healthy-subject pharmacokinetic studies the estimated effective half-life was about 88 hours after a 10 mg dose (around 124 hours at 5 mg), with two depot metabolites accounting for more than 98% of total exposure at steady state. This protracted profile is why glepaglutide can be dosed once or twice weekly rather than daily.
How do you reconstitute Glepaglutide?expand_more
On this educational model, draw 1.0 mL of bacteriostatic water and add it slowly down the wall of a 20 mg glepaglutide vial, then swirl gently until clear. This yields 20 mg/mL, so each insulin-syringe unit holds 200 mcg and a 10 mg dose equals 50 units (0.5 mL). Store the solution refrigerated at 2-8 °C, protected from light, do not freeze, and use it within the validated in-use window. In clinical trials glepaglutide is reconstituted in a dedicated pen/autoinjector.
How does Glepaglutide compare to teduglutide?expand_more
Both are GLP-2 receptor agonists that promote intestinal mucosal growth and absorption to reduce parenteral support in short bowel syndrome. The key difference is dosing frequency: teduglutide (Gattex/Revestive) is approved and injected once daily, whereas glepaglutide's depot pharmacokinetics allow once- or twice-weekly injection. Glepaglutide remains investigational (FDA Complete Response Letter, December 2024), while teduglutide is already approved, so they are not interchangeable and any comparison here is educational only.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Glepaglutide, plus the universal dosing calculator.
Academic References & Study Citations
Jeppesen PB, Vanuytsel T, Subramanian S, et al. Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial. Gastroenterology. 2025;168(4):701-713.e6. View Scientific Paper →
Naimi RM, Hvistendahl M, Enevoldsen LH, et al. Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2019;4(5):354-363. View Scientific Paper →
Agersnap M, Sonne K, Knudsen KM, Knudsen CB, Berner-Hansen M. Pharmacokinetics of Glepaglutide, A Long-Acting Glucagon-Like Peptide-2 Analogue: A Study in Healthy Subjects. Clin Drug Investig. 2022;42(12):1093-1100. View Scientific Paper →
Agersnap M, Sonne K, Knudsen KM, Sulowicz W. Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment. Clin Pharmacokinet. 2023;62(4):645-651. View Scientific Paper →
Naimi RM, Hvistendahl M, Nerup N, et al. Effects of glepaglutide, a long-acting glucagon-like peptide-2 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial. JPEN J Parenter Enteral Nutr. 2023. View Scientific Paper →
Naimi RM, Hvistendahl M, Nerup N, et al. Effects of glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, on markers of liver status in patients with short bowel syndrome: findings from a randomised phase 2 trial. EBioMedicine. 2019;46:444-451. View Scientific Paper →
U.S. National Library of Medicine. Efficacy and Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome (SBS). ClinicalTrials.gov identifier NCT03690206. View Scientific Paper →
Drugs.com. Glepaglutide: What is it and is it FDA approved? (regulatory development history). View Scientific Paper →
Zealand Pharma. U.S. Food and Drug Administration issues Complete Response Letter for the glepaglutide New Drug Application for the treatment of short bowel syndrome (December 2024 press release). View Scientific Paper →