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.
Apraglutide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Apraglutide (FE 203799) is a long-acting GLP-2 receptor agonist designed to heal and regrow the intestinal lining in short bowel syndrome with intestinal failure (SBS-IF). Four amino-acid substitutions make it resistant to DPP-4 and very slowly cleared, so a single subcutaneous injection works for a full week, unlike daily teduglutide (PMID 32075870, 37316329). Activating GLP-2 receptors increases villus height and absorptive surface, slows transit, and improves absorption of fluid, sodium, and calories, reducing reliance on parenteral nutrition. The pivotal Apraglutide dosage is 5 mg once weekly for adults at least 50 kg (2.5 mg if under 50 kg). In the phase 3 STARS trial (NCT04627025), once-weekly apraglutide cut parenteral-support volume by 25.5% versus 12.5% with placebo at week 24. Apraglutide remains investigational and is not approved by the FDA or EMA; the figures here are educational only, not medical advice.
Reconstitute: Add 1.5 mL bacteriostatic water → 6.67 mg/mL concentration.
Typical dose: 5 mg SC once weekly (>=50 kg); 2.5 mg once weekly (<50 kg)
Easy measuring: At 6.67 mg/mL, 1 unit = 0.01 mL = 0.0667 mg (67 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at -20 °C; once reconstituted, keep refrigerated at 2-8 °C and use within the labeled beyond-use period (typically ~2-4 weeks). Protect from light; do not freeze the reconstituted solution and avoid vigorous shaking.
Half-life: ~30 hours in patients with short bowel syndrome and ~70 hours in healthy volunteers; DPP-4-resistant with very low clearance, enabling once-weekly dosing.
Route: Subcutaneous injection once weekly, rotating sites (abdomen, thigh, or upper arm).
Status: Investigational — not approved by the FDA or EMA; FDA requested a confirmatory phase 3 trial in 2025.
About Apraglutide
Apraglutide is a next-generation GLP-2 receptor agonist developed (originally as FE 203799) to regrow and heal the intestinal lining in short bowel syndrome. Unlike the first-in-class GLP-2 analog teduglutide, which must be injected daily, apraglutide's engineered resistance to enzymatic breakdown and very slow clearance allow once-weekly subcutaneous administration [1][2]. The clinically studied route is genuinely subcutaneous, so the reconstitution figures below mirror how the drug is actually delivered rather than being a modeling convention.\n\nThis guide models a 10 mg vial reconstituted with 1.5 mL of bacteriostatic water (about 6.7 mg/mL), so the standard 5 mg weekly dose lands at roughly 75 units on a U-100 insulin syringe and the lower-body-weight 2.5 mg dose at about 37-38 units. The established weight-based Apraglutide dosage is 5 mg once weekly for adults weighing 50 kg or more and 2.5 mg once weekly for those under 50 kg [3][5][8].\n\nFrequency: Once weekly, on the same day each week, rotating subcutaneous sites (abdomen, thigh, upper arm). Apraglutide is investigational and is NOT approved by the FDA or EMA; everything here is an educational reference only, not medical advice [7].
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 1.5 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 10 mg apraglutide vial; aim away from the lyophilized powder and do not shake.
Let the vial sit, then swirl gently until the solution is completely clear; this yields about 6.7 mg/mL (~66.7 mcg per U-100 unit).
Swab the stopper and draw your weekly dose: about 75 units for 5 mg (>=50 kg) or about 37-38 units for 2.5 mg (<50 kg).
Inject subcutaneously into the abdomen, thigh, or upper arm once weekly, rotating sites; store the reconstituted vial refrigerated at 2-8 °C and discard per beyond-use guidance.
Interactive Apraglutide Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 1.5 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 1.5mL water yields 6.67 mg/mL. To evaluate a 250mcg dose, pull to 3.8 units (4 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) |
|---|---|---|
| Lower body weight (<50 kg) — once weekly | 2500 mcg (2.5 mg) | 38 units (0.38 mL) |
| Standard adult (>=50 kg) — once weekly | 5000 mcg (5 mg) | 75 units (0.75 mL) |
| High-dose research arm (10 mg, studied only — split across two injections) | 10000 mcg (10 mg) | 150 units (1.50 mL) |
Administration guidelines: Refer to guidelines | 1.5 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Apraglutide, 10 mg each):
- check8-week course at 5 mg/week: 40 mg total = 4 vials
- check12-week course at 5 mg/week: 60 mg total = 6 vials
- check16-week course at 5 mg/week: 80 mg total = 8 vials
- checkEach 10 mg vial supplies two 5 mg weekly doses (or four 2.5 mg doses)
Insulin Syringes (U-100):
- checkOne injection per week: ~10 syringes for an 8-week course (with spares)
- check~14 syringes for a 12-week course
- check~18 syringes for a 16-week course
- check0.5 mL (50-unit) syringes comfortably hold the ~75-unit 5 mg dose if drawn in one pull, or use a 1 mL (100-unit) syringe
Bacteriostatic Water (3 mL or 30 mL bottles): Use 1.5 mL per vial for reconstitution.
- check8-week course: 4 vials x 1.5 mL = 6 mL
- check12-week course: 6 vials x 1.5 mL = 9 mL
- check16-week course: 8 vials x 1.5 mL = 12 mL
- checkOne 30 mL bottle covers an entire 8-, 12-, or 16-week course
Alcohol Swabs: Clean the vial stopper and injection site before each dose.
- check~2 swabs per weekly injection (vial top + skin)
- check8-week course: ~16 swabs; 12-week: ~24 swabs; 16-week: ~32 swabs
- checkOne 100-count box covers all course lengths with margin
Mechanism of Action (MOA)
Apraglutide is a 33-amino-acid synthetic peptide analog of human glucagon-like peptide-2 (GLP-2), the gut hormone released by intestinal L-cells after eating. Its sequence carries four substitutions relative to native GLP-2 — written as [Gly2, Nle10, D-Phe11, Leu16]hGLP-2(1-33)-NH2 — identified through structure-activity optimization of lipophilic residues at positions 11 and 16 [1]. The glycine at position 2 blocks cleavage by dipeptidyl peptidase-4 (DPP-4), the enzyme that inactivates native GLP-2 within minutes, while the lipophilic substitutions drive high plasma-protein binding and unusually low systemic clearance. Together these changes produce slow subcutaneous absorption, a long terminal half-life, and sustained receptor exposure without any lipidation, PEGylation, or fusion partner [1][2].\n\nMechanistically, apraglutide binds and activates the GLP-2 receptor, a class B G-protein-coupled receptor expressed on subepithelial myofibroblasts, enteric neurons, and enteroendocrine cells of the small and large intestine. Receptor activation triggers cAMP signaling and downstream release of trophic mediators (including IGF-1, IGF-2, keratinocyte growth factor, and nitric oxide) that act on the crypt-villus axis. The net effect is intestinotrophic: increased villus height and crypt depth, expansion of absorptive mucosal surface area, enhanced intestinal blood flow, slowed gastric emptying and transit, and reduced secretion — all raising the gut's capacity to absorb fluid, sodium, and nutrients. Plasma citrulline, a biomarker of functional enterocyte mass, rises measurably during treatment [2][3].\n\nPharmacokinetics: after subcutaneous injection apraglutide is absorbed slowly, with mean clearance of roughly 16.5-20.7 L/day and a volume of distribution of about 55-105 L in healthy volunteers [2]. Its terminal half-life averages around 30 hours in patients with short bowel syndrome and is longer (on the order of ~70 hours) in healthy volunteers, far exceeding teduglutide's ~2-3 hours; this is precisely what permits a single weekly injection rather than daily dosing [1][2]. In phase 1/2 metabolic-balance work, the maximal pharmacodynamic (citrulline) response was reached at the 5 mg weekly dose, supporting 5 mg as the pivotal dose, with effects persisting 10-17 days after the final injection [2][3].\n\nClinically apraglutide is dosed by body weight — 5 mg once weekly at 50 kg or above, 2.5 mg once weekly below 50 kg — to reduce or eliminate the need for parenteral nutrition and intravenous fluids in SBS-IF, and it has also been investigated for acute gastrointestinal graft-versus-host disease [3][5]. The subcutaneous reconstitution scheme on this page reflects the genuine delivery route; the doses, concentrations, and unit conversions are provided for education only. Apraglutide is not an approved drug, and in 2025 the FDA requested an additional confirmatory phase 3 trial before it could be approved [7].
Clinical Trial Efficacy Highlights
- starHargrove and colleagues (2020, Journal of Pharmacology and Experimental Therapeutics) pharmacologically characterized apraglutide and showed it has very low clearance, a long elimination half-life, and high plasma-protein binding compared with the GLP-2 analogs teduglutide and glepaglutide, with potent intestinotrophic activity in preclinical models — the basis for once-weekly dosing [1].
- starBolognani and colleagues (2023, JPET) studied healthy volunteers given 1, 5, or 10 mg subcutaneous apraglutide weekly for six administrations and found predictable, dose-dependent pharmacokinetics (clearance ~16.5-20.7 L/day, volume of distribution ~55-105 L); the 5 mg dose induced the maximal pharmacodynamic citrulline response, with sustained effects 10-17 days after the last dose [2].
- starEliasson and colleagues (2022, JPEN) ran an open-label phase 1/2 metabolic-balance trial in 8 adults with short bowel syndrome; 5 mg once-weekly apraglutide for 4 weeks significantly increased intestinal fluid absorption by 741 g/day (95% CI 194-1287; P=0.015) and energy absorption by 1095 kJ/day (95% CI 196-1994; P=0.024), plus sodium and potassium absorption [3].
- starIn a placebo-controlled, randomized, crossover phase 2 trial, Eliasson and colleagues (2022, JPEN) showed that once-weekly 5 mg and 10 mg apraglutide significantly increased urine output (adjusted mean +714 mL/day at 5 mg and +795 mL/day at 10 mg) versus placebo in SBS-IF, confirming improved intestinal fluid absorption [4].
- starThe phase 3 STARS trial (NCT04627025) randomized 164 adults with SBS-IF 2:1 to once-weekly subcutaneous apraglutide or placebo; at week 24 apraglutide met its primary endpoint with a 25.5% relative reduction in weekly parenteral-support volume versus 12.5% for placebo (P=0.001), and more apraglutide patients achieved at least one additional day per week off parenteral support (43.0% vs 27.5%; P=0.040) [5].
- starIn STARS, a higher proportion of apraglutide-treated patients reached total enteral autonomy by week 24 (6.4% vs 0% with placebo), and the drug was well tolerated with a low discontinuation rate due to adverse events (3.6% vs 1.9%) [5].
- starGreig and colleagues (2024, Journal of Clinical Pharmacology) characterized the single-dose pharmacokinetics and tolerability of apraglutide in individuals with normal and impaired renal function, helping define exposure across renal-function strata in this comorbid SBS population [6].
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 and reflect the drug's trophic action on the gut: abdominal pain or distension, nausea, vomiting, and flatulence, particularly early in treatment [3][5].
- warningFluid overload and peripheral edema can occur because GLP-2 agonism enhances intestinal fluid and sodium absorption; this warrants caution and monitoring in patients with cardiac or renal compromise [4][5].
- warningStoma-related complications, including stomal swelling and changes in stoma size or output, are reported in SBS patients with a stoma and may require ostomy-appliance adjustment.
- warningSubcutaneous injection-site reactions (redness, swelling, discomfort) can occur; rotating sites between the abdomen, thigh, and upper arm reduces irritation.
- warningGLP-2 is intestinotrophic, so as a class GLP-2 receptor agonists carry a theoretical risk of stimulating growth of intestinal or colorectal polyps or neoplasia; the related drug teduglutide carries colonoscopy-surveillance recommendations, and similar vigilance is prudent with apraglutide.
- warningHepatobiliary and pancreatic events such as gallbladder/biliary disease, cholecystitis, and pancreatitis are recognized class warnings for GLP-2 agonists and warrant clinical monitoring.
- warningIn the SBS population, risks include intestinal or stomal obstruction and central-venous catheter-related complications; apraglutide does not eliminate the underlying need for careful SBS management.
- warningRegulatory and research status: apraglutide is investigational and NOT approved by the FDA or EMA; in STARS, delivered exposure was lower than planned due to dose-preparation issues, and in 2025 the FDA requested a confirmatory phase 3 trial. Long-term safety is not established, and all dosing here is educational only [5][7].
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 Apraglutide dosage?expand_more
Across the phase 1-3 program, the typical Apraglutide dosage is 5 mg subcutaneously once weekly for adults weighing at least 50 kg, and 2.5 mg once weekly for those under 50 kg. A 10 mg dose was also studied in early trials but is research-only. Dosing is fixed and weight-based rather than titrated. Apraglutide is investigational; these figures are educational, not a prescription.
Is Apraglutide FDA approved?expand_more
No. As of 2026, apraglutide is NOT approved by the FDA or the EMA for any indication. Despite meeting its primary endpoint in the phase 3 STARS trial, the FDA in April 2025 requested an additional confirmatory phase 3 trial before an approval could be granted, partly because delivered drug exposure in STARS was lower than planned. It remains an investigational compound.
How do you reconstitute Apraglutide?expand_more
For the educational model on this page, draw 1.5 mL of bacteriostatic water and inject it slowly down the inner wall of a 10 mg vial, then swirl (do not shake) until clear. This gives about 6.7 mg/mL, or roughly 66.7 mcg per unit on a U-100 insulin syringe, so a 5 mg dose is about 75 units and a 2.5 mg dose about 37-38 units. Refrigerate the reconstituted solution at 2-8 °C.
What is Apraglutide's half life?expand_more
Apraglutide has a long terminal half-life — averaging roughly 30 hours in patients with short bowel syndrome and on the order of ~70 hours in healthy volunteers — far longer than teduglutide's ~2-3 hours. Four amino-acid substitutions make it resistant to DPP-4 and give it very low clearance and high protein binding, which is why a single subcutaneous injection lasts a full week.
How is Apraglutide different from teduglutide?expand_more
Both are GLP-2 receptor agonists used for short bowel syndrome, but apraglutide is engineered for much slower clearance and DPP-4 resistance, allowing once-weekly subcutaneous dosing versus teduglutide's daily injection. Apraglutide is investigational and not yet approved, whereas teduglutide (Gattex/Revestive) is an approved GLP-2 therapy. They share the same intestinotrophic mechanism and class side-effect profile.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Apraglutide, plus the universal dosing calculator.
Academic References & Study Citations
Hargrove DM, Alagarsamy S, Croston G, et al. Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome. J Pharmacol Exp Ther. 2020;373(2):193-203. PMID 32075870. View Scientific Paper →
Bolognani F, et al. Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers. J Pharmacol Exp Ther. 2023;386(2):129-137. PMID 37316329. View Scientific Paper →
Eliasson J, et al. Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial. JPEN J Parenter Enteral Nutr. 2022. PMID 35233802. View Scientific Paper →
Eliasson J, 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 J Parenter Enteral Nutr. 2022. View Scientific Paper →
STARS: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial of Apraglutide in Adults With Short Bowel Syndrome With Intestinal Failure on Parenteral Support (NCT04627025). ClinicalTrials.gov. View Scientific Paper →
Greig CJ, et al. Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long-Acting, Synthetic Glucagon-Like Peptide-2 Analog, in Individuals With Impaired Renal Function. J Clin Pharmacol. 2024. doi:10.1002/jcph.2423. View Scientific Paper →
Ironwood Pharmaceuticals regulatory update: FDA requires a confirmatory phase 3 trial before approval of apraglutide for SBS-IF (April 2025). Medthority news summary. View Scientific Paper →
Safety, Efficacy, and Pharmacodynamics of FE 203799 (Apraglutide) in Short Bowel Syndrome Subjects on Parenteral Support — Phase 2 (NCT03415594). ClinicalTrials.gov. View Scientific Paper →