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.
Efocipegtrutide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Efocipegtrutide (HM15211, the LAPS Triple Agonist) is an investigational once-weekly peptide that activates the GLP-1, GIP, and glucagon receptors at the same time, built on Hanmi's LAPScovery Fc-fusion platform for extended half-life (NCT04505436). GLP-1 and GIP signaling curb appetite and improve glucose handling, while the glucagon arm raises energy expenditure and drives hepatic fat oxidation, making it a candidate for metabolic-associated steatohepatitis (MASH) and obesity. The Phase 2 dosage is 2, 4, or 6 mg subcutaneously once weekly, given as fixed dose arms without titration; earlier Phase 1 studies used 0.01-0.12 mg/kg (PMID 37028504, NCT03374241). It is not approved by the FDA or EMA and is studied as a research compound only. The reconstitution and dosing figures here model a real subcutaneous route as an educational reference, not medical advice.
Reconstitute: Add 2 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: 2-6 mg SC once weekly
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Lyophilized/research powder stored frozen at −20 °C and protected from light; reconstituted solution refrigerated at 2-8 °C and used within ~4 weeks. Clinical-trial material is supplied as a refrigerated sterile solution in pre-filled syringes (2-8 °C); do not freeze reconstituted or liquid product.
Half-life: Extended terminal half-life on the order of several days via Fc/FcRn recycling, supporting once-weekly subcutaneous dosing; exact published values are limited.
Route: Subcutaneous injection (genuine clinical route), 2-6 mg once weekly in Phase 2.
Status: Investigational; not FDA/EMA approved. FDA Fast Track for MASH; orphan designations for IPF, PBC, PSC.
About Efocipegtrutide
Efocipegtrutide (HM15211) is a once-weekly GLP-1/GIP/glucagon triple-receptor agonist that Hanmi Pharmaceutical has advanced through Phase 1 and Phase 2 studies for non-alcoholic/metabolic-associated steatohepatitis (NASH/MASH) and obesity [1][5]. This page explains the Efocipegtrutide dosage used in clinical research and models it as a subcutaneous reconstitution protocol so the unit math is easy to follow on a U-100 insulin syringe. Unlike oral or topical compounds, Efocipegtrutide's real-world route is genuinely subcutaneous injection, so the reconstitution figures below map directly onto how the drug is administered in trials.\n\nThe registered Phase 2 program (NCT04505436, HM-TRIA-201) tested 2 mg, 4 mg, and 6 mg once weekly as fixed parallel-dose arms with no titration period [1][2]. To mirror the site's titration-style layout, this guide presents those same three doses as escalating phases, but be clear that in the trial each participant stayed on a single fixed dose. Modeling a 20 mg vial reconstituted with 2.0 mL of bacteriostatic water yields 10 mg/mL (100 mcg per insulin-syringe unit), so 2 mg ≈ 20 units, 4 mg ≈ 40 units, and 6 mg ≈ 60 units, all measurable on one standard U-100 syringe.\n\nFrequency: Once weekly, subcutaneously, on the same day each week. Efocipegtrutide is not FDA- or EMA-approved and is presented here for educational purposes only, not as medical advice.
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 2.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 20 mg Efocipegtrutide vial; aim the stream away from the powder and do not shake.
Gently swirl or roll the vial until the solution is completely clear; the result is a 10 mg/mL concentration (100 mcg per insulin-syringe unit).
Store refrigerated at 2-8 °C and draw the prescribed number of units per weekly dose (2 mg ≈ 20 units, 4 mg ≈ 40 units, 6 mg ≈ 60 units), all of which fit in one U-100 syringe.
Swab the injection site, inject subcutaneously into the abdomen at a consistent weekly time, rotate sites to limit irritation, and discard the reconstituted vial after ~4 weeks; Efocipegtrutide is investigational and these figures are an educational reference only.
Interactive Efocipegtrutide Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 2mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 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) |
|---|---|---|
| Weeks 1-4: Starting dose (2 mg arm) | 2000 mcg (2 mg) | 20 units (0.20 mL) |
| Weeks 5-8: Mid dose (4 mg arm) | 4000 mcg (4 mg) | 40 units (0.40 mL) |
| Weeks 9+: Target dose (6 mg arm) | 6000 mcg (6 mg) | 60 units (0.60 mL) |
Administration guidelines: Refer to guidelines | 2 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 (Efocipegtrutide, 20 mg each):
- check8-week course (escalating to 4 mg): ~24 mg total — about 2 vials
- check12-week course (escalating to 6 mg): ~48 mg total — about 3 vials
- check16-week course (escalating to 6 mg): ~72 mg total — about 4 vials
- checkEach 20 mg vial yields ~3 weekly doses at the 6 mg target dose
Insulin Syringes (U-100):
- checkOne 0.5 mL U-100 syringe per weekly injection
- check8-week course: ~8-10 syringes (including spares)
- check12-week course: ~12-14 syringes
- check16-week course: ~16-20 syringes
Bacteriostatic Water (30 mL bottles): Use 2 mL per vial for reconstitution.
- check8-week course: ~4 mL (2 vials) — one 30 mL bottle is ample
- check12-week course: ~6 mL (3 vials)
- check16-week course: ~8 mL (4 vials)
- checkA single 30 mL bottle covers all three course lengths
Alcohol Swabs: Clean the vial stopper and injection site before each use.
- check2-3 swabs per weekly injection (stopper + site)
- check8-week course: ~24 swabs
- check12-week course: ~36 swabs
- check16-week course: ~48 swabs
Mechanism of Action (MOA)
Efocipegtrutide is a single-chain peptide unimolecular agonist engineered to engage three distinct class-B G-protein-coupled receptors at once: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR) [5][7]. Each arm contributes a complementary metabolic effect. GLP-1R activation suppresses appetite, slows gastric emptying, and stimulates glucose-dependent insulin secretion; GIPR activation adds further insulinotropic and lipid-handling effects; and GCGR activation raises energy expenditure, promotes hepatic fatty-acid β-oxidation, and reduces de novo lipogenesis [5][6]. The glucagon component is the differentiating feature versus pure GLP-1 or GLP-1/GIP dual agonists, and Hanmi's preclinical and mechanistic work attributes much of the compound's direct anti-steatotic and anti-fibrotic liver action to that glucagon engagement [5].\n\nThe molecule is built on Hanmi's LAPScovery (Long-Acting Protein/Peptide Discovery) platform. The triple-agonist peptide is covalently conjugated through a non-peptidyl flexible linker to an aglycosylated Fc fragment derived from human immunoglobulin G4 [5][7]. This Fc moiety retains pH-dependent neonatal Fc receptor (FcRn) binding, the same vascular-endothelial recycling mechanism that gives antibodies their long plasma residence. FcRn-mediated salvage, combined with reduced renal clearance from the larger conjugate size, produces an extended terminal half-life on the order of several days, which is why a single subcutaneous dose maintains exposure suitable for once-weekly administration [3][5].\n\nPharmacokinetics: in the first-in-human single-ascending-dose study (NCT03374241), 0.01 to 0.12 mg/kg was given subcutaneously to healthy obese subjects, and the PK profile confirmed a prolonged half-life appropriate for weekly dosing, with adverse events (chiefly gastrointestinal and nervous-system, dose-dependent) rising at the highest cohorts [3]. The 12-week multiple-dose Phase 1b/2a study in obese subjects with NAFLD (NCT03744182) dosed 0.01-0.08 mg/kg weekly and reported dose-dependent reductions in hepatic fat content and body weight [4]. These data, alongside preclinical NASH models, supported the fixed 2/4/6 mg weekly doses chosen for the Phase 2 HM-TRIA-201 trial, which uses absolute milligram doses rather than weight-based dosing [1][2].\n\nThe primary clinical objective in MASH is histologic resolution of steatohepatitis without worsening of fibrosis, reflecting the hypothesis that combined incretin and glucagon signaling can reduce hepatic fat, inflammation, and fibrogenesis simultaneously [1][2]. Because no full peer-reviewed efficacy paper has yet been published, the available picture rests on trial registries, conference reports, and the published study-design/rationale paper [2][6]. Efocipegtrutide remains investigational; the subcutaneous reconstitution scheme here is an educational measurement convention, not a clinically authorized regimen.
Clinical Trial Efficacy Highlights
- starThe Phase 2 HM-TRIA-201 trial (NCT04505436) is a randomized, double-blind, placebo-controlled, parallel-group study of 2 mg, 4 mg, and 6 mg Efocipegtrutide once weekly versus placebo in roughly 215-217 patients with biopsy-confirmed NASH (fibrosis F1-F3), with the primary endpoint being resolution of steatohepatitis at 12 months without worsening of fibrosis; no dose-titration period is included [1][2].
- starThe published study-design and rationale paper (Abdelmalek MF, Suzuki A, Sanchez W, Lawitz E, et al., Contemporary Clinical Trials 2023; PMID 37028504) describes HM15211 as a novel long-acting GLP-1/glucagon/GIP triple incretin agonist that showed promising efficacy in in vitro and preclinical rodent NASH models and a manageable safety profile in Phase 1, motivating the adaptive 52-week Phase 2 design [2].
- starThe first-in-human single-ascending-dose study (NCT03374241) administered 0.01, 0.02, 0.04, 0.08, and 0.12 mg/kg subcutaneously to 41 healthy obese subjects; the pharmacokinetic profile was suitable for once-weekly dosing, and adverse events (predominantly gastrointestinal and nervous-system) increased in a dose-dependent fashion at the higher cohorts [3].
- starThe 12-week multiple-dose Phase 1b/2a study (NCT03744182) enrolled 66 obese subjects with NAFLD across 0.01-0.08 mg/kg weekly arms plus placebo and reported dose-dependent reductions in hepatic fat content and body weight, the proof-of-concept data that informed the Phase 2 dose selection [4].
- starHanmi's mechanistic and preclinical work indicates that the glucagon-receptor arm of the triple agonist contributes directly to anti-inflammatory and anti-fibrotic effects in the liver, supporting the rationale for combining glucagon signaling with GLP-1/GIP incretin action in MASH [5].
- starEfocipegtrutide has received FDA Fast Track designation for MASH and orphan-drug designations from the FDA and EMA for idiopathic pulmonary fibrosis (IPF), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), reflecting regulatory interest across fibrotic indications [5].
- starIndependent review of the MASLD/MASH pipeline notes that, as of its publication, no peer-reviewed articles presenting full efficacy results for efocipegtrutide were available, so the evidence base currently rests on trial registries, conference abstracts, and the study-design literature rather than completed pivotal outcomes [6][7].
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 (nausea, vomiting, diarrhea, decreased appetite) are the most common class effects of GLP-1/GIP/glucagon agonists and increased in a dose-dependent manner in the Efocipegtrutide single-ascending-dose study, especially at higher cohorts [3].
- warningNervous-system adverse events (e.g., headache, dizziness) were also reported as dose-dependent in early-phase dosing and may overlap with GI symptoms during dose escalation [3].
- warningThe glucagon-receptor component can raise hepatic glucose output and energy expenditure; glucose, heart rate, and blood pressure are monitored in trials, and the long-term metabolic impact of sustained glucagon agonism in humans is not fully characterized [5][6].
- warningAs a subcutaneous injectable, it can cause injection-site reactions (redness, itching, transient nodules); rotating abdominal injection sites helps limit local irritation.
- warningGLP-1-class agents carry warnings for pancreatitis, gallbladder events, and (in rodent studies of related drugs) thyroid C-cell effects; these have not been specifically established or excluded for Efocipegtrutide given limited published human data [6][7].
- warningNo full peer-reviewed safety dataset has been published; the human safety profile is described only as 'manageable' from Phase 1, so rare or long-term risks remain undefined [2][6].
- warningIt should not be combined with other incretin agonists, insulin secretagogues, or weight-loss agents outside a supervised trial because of additive GI and glycemic effects; interactions are not formally characterized.
- warningRegulatory/research status: Efocipegtrutide is NOT approved by the FDA, EMA, or any major regulator for any indication. It is an investigational, clinical-stage compound and is presented here for educational purposes only, not for human use.
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 Efocipegtrutide dosage?expand_more
In the Phase 2 NASH/MASH program (NCT04505436, HM-TRIA-201), the typical Efocipegtrutide dosage is 2 mg, 4 mg, or 6 mg given by subcutaneous injection once weekly, as fixed parallel-dose arms with no titration. Earlier Phase 1 studies used weight-based dosing of 0.01-0.12 mg/kg. These are research doses only; Efocipegtrutide is investigational and not approved for human use.
Is Efocipegtrutide FDA approved?expand_more
No. Efocipegtrutide (HM15211) is not approved by the FDA, the EMA, or any other regulator for any indication. It is a clinical-stage investigational drug. It has received FDA Fast Track designation for MASH and orphan-drug designations for IPF, PBC, and PSC, but those are development incentives, not approvals. Everything on this page is educational, not medical advice.
How do you reconstitute Efocipegtrutide?expand_more
For this educational model, draw 2.0 mL of bacteriostatic water and add it slowly down the wall of a 20 mg vial, then swirl gently until clear. That gives 10 mg/mL, or 100 mcg per unit on a U-100 insulin syringe, so 2 mg is about 20 units, 4 mg about 40 units, and 6 mg about 60 units. Store the reconstituted solution refrigerated at 2-8 °C and use within roughly four weeks.
What is the Efocipegtrutide half life?expand_more
Efocipegtrutide is engineered for a long half-life through its IgG4-derived Fc fragment, which uses FcRn recycling and reduced renal clearance to extend plasma residence. Published Phase 1 data describe a prolonged terminal half-life on the order of several days, which is what allows once-weekly subcutaneous dosing. Exact peer-reviewed half-life values are limited because full clinical results have not yet been published.
Can Efocipegtrutide be stacked with other peptides?expand_more
There is no clinical evidence supporting stacking Efocipegtrutide with other compounds, and it should not be combined with other GLP-1/GIP agonists, insulin secretagogues, or weight-loss agents outside a supervised trial. As a triple agonist it already covers GLP-1, GIP, and glucagon pathways, so adding similar agents would mainly compound gastrointestinal and glycemic effects. It remains investigational and is presented for educational purposes only.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Efocipegtrutide, plus the universal dosing calculator.
Academic References & Study Citations
ClinicalTrials.gov. Study to Evaluate Efficacy, Safety and Tolerability of HM15211 (Efocipegtrutide) in Subjects With Biopsy-Confirmed NASH (HM-TRIA-201). Identifier NCT04505436. Sponsor: Hanmi Pharmaceutical. View Scientific Paper →
Abdelmalek MF, Suzuki A, Sanchez W, Lawitz E, et al. A phase 2, adaptive randomized, double-blind, placebo-controlled, multicenter, 52-week study of HM15211 in patients with biopsy-confirmed NASH — study design and rationale of the HM-TRIA-201 study. Contemporary Clinical Trials. 2023. PMID 37028504. View Scientific Paper →
ClinicalTrials.gov. A First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Ascending Dose of HM15211 (Efocipegtrutide) in Healthy Obese Subjects. Identifier NCT03374241. View Scientific Paper →
ClinicalTrials.gov. A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of HM15211 (Efocipegtrutide) in Obese Subjects With NAFLD. Identifier NCT03744182. View Scientific Paper →
Hanmi Pharmaceutical. Efocipegtrutide (HM15211) — Pipeline: LAPScovery triple agonist; FcRn-mediated long action; Fast Track and orphan-drug designations. View Scientific Paper →
Bołdys A, Bułdak Ł, Maligłówka M, Surma S, Okopień B. Potential Therapeutic Strategies in the Treatment of Metabolic-Associated Fatty Liver Disease. PMC10608225 (triple incretin receptor agonists, incl. efocipegtrutide). View Scientific Paper →
Efocipegtrutide — Wikipedia (GLP-1/GIP/glucagon triple receptor agonist; investigational for obesity and NASH). View Scientific Paper →