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.
Efinopegdutide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Efinopegdutide (MK-6024, JNJ-64565111, HM12525A) is an investigational once-weekly GLP-1/glucagon receptor dual co-agonist developed by Hanmi, Janssen and Merck for obesity, type 2 diabetes and fatty-liver disease (NASH/MASH). The GLP-1 arm curbs appetite and slows gastric emptying, while the glucagon arm raises energy expenditure and drives hepatic fat oxidation, making liver-fat clearance its standout effect (PMID 37355043). The most-studied doses are 5, 7.4 and 10 mg subcutaneously once weekly, with 10 mg the target reached over an 8-week titration. In a Phase 2a NAFLD trial, 10 mg weekly cut liver fat by 72.7% versus 42.3% for semaglutide 1 mg; in a Phase 2 obesity trial it produced 11.8% weight loss over 26 weeks (PMID 33475255). It is genuinely injected subcutaneously once weekly. Efinopegdutide is not FDA- or EMA-approved; it is investigational and provided here for educational reference only.
Reconstitute: Add 2 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: 5-10 mg SC once weekly (10 mg target)
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2-8 °C, protected from light, and used within ~28 days. Do not freeze the reconstituted solution; discard if cloudy or if particulates appear.
Half-life: Roughly 5 days (~100-115 hours; up to ~7 days in some data) due to Fc-carrier conjugation; Tmax ~4-6 days, supporting fixed once-weekly subcutaneous dosing.
Route: Subcutaneous once weekly (abdomen, thigh or upper arm); studied doses 5/7.4/10 mg, with 10 mg the target after an 8-week titration.
Status: Investigational; not FDA- or EMA-approved. FDA Fast Track for NASH (2023), Phase 2b underway. Research/educational use only, not medical advice.
About Efinopegdutide
Efinopegdutide is a GLP-1/glucagon receptor dual co-agonist (development codes MK-6024, JNJ-64565111 and HM12525A) studied as a once-weekly subcutaneous injection for obesity, type 2 diabetes and fatty-liver disease [1][2]. Unlike many compounds catalogued on this site, efinopegdutide is genuinely an injectable: every published clinical trial delivered it subcutaneously once weekly, so the reconstitution model below reflects its real-world route. The most-studied Efinopegdutide dosage is 5, 7.4 or 10 mg once weekly, with 10 mg the target dose reached after an 8-week titration in the NAFLD program [1][3].\n\nThis guide models a 20 mg vial reconstituted with 2.0 mL of bacteriostatic water (10 mg/mL) so the studied doses map cleanly onto a U-100 insulin syringe: 5 mg ≈ 50 units, 7.4 mg ≈ 74 units, and 10 mg ≈ 100 units (one full syringe). Protocols typically begin at 5 mg to build gastrointestinal tolerance, step up to 7.4 mg, then hold at the 10 mg maintenance dose used in the liver-fat and weight-loss trials [1][2].\n\nFrequency: Once weekly, on the same day each week, rotating injection sites between the abdomen, thigh and upper arm. Efinopegdutide is investigational and not approved by the FDA or EMA; the figures here are an educational reference only, not 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 wall of the 20 mg efinopegdutide vial; do not aim the stream directly at the lyophilized powder, and avoid vigorous shaking.
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 the reconstituted vial refrigerated at 2-8 °C and draw the prescribed number of units per weekly dose (5 mg ≈ 50 units, 7.4 mg ≈ 74 units, 10 mg ≈ 100 units, which is one full U-100 syringe).
Swab the injection site (abdomen, thigh or upper arm), inject subcutaneously once weekly on the same day, rotate sites between injections, and discard the vial 28 days after reconstitution.
Interactive Efinopegdutide 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 — titration start (build GI tolerance) | 5000 mcg (5 mg) | 50 units (0.50 mL) |
| Weeks 5-8 — intermediate step | 7400 mcg (7.4 mg) | 74 units (0.74 mL) |
| Week 9+ — target/maintenance dose | 10000 mcg (10 mg) | 100 units (1.00 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 (Efinopegdutide, 20 mg each):
- check8-week course (titration through 7.4 mg) ≈ 3-4 vials (~60-80 mg)
- check12-week course (reaching 10 mg maintenance) ≈ 5-6 vials (~100-120 mg)
- check16-week course ≈ 7-8 vials (~140-160 mg); partial-vial waste and the 28-day reconstituted shelf life raise the count slightly
Insulin Syringes (U-100):
- checkOnce-weekly dosing: 1 syringe per dose
- check8 weeks ≈ 8-10 syringes; 12 weeks ≈ 12-14 syringes
- check16 weeks ≈ 16-18 syringes; the 10 mg dose (≈100 units) fills one full U-100 syringe
Bacteriostatic Water (30 mL bottles): Use 2 mL per 20 mg vial for reconstitution.
- check8 weeks (~4 vials) ≈ 8 mL
- check12 weeks (~6 vials) ≈ 12 mL
- check16 weeks (~8 vials) ≈ 16 mL — one 30 mL bottle covers a full course
Alcohol Swabs:
- check2 swabs per weekly dose (vial top + injection site)
- check8 weeks ≈ 16-24 swabs; 12 weeks ≈ 24-32 swabs
- check16 weeks ≈ 32-48 swabs; keep extras for re-swabbing the multi-use vial
Mechanism of Action (MOA)
Efinopegdutide is a single-molecule (unimolecular) peptide dual agonist built on a glucagon/GLP-1 hybrid sequence and conjugated through a flexible linker to a non-glycosylated human immunoglobulin Fc carrier (Hanmi's long-acting LAPSCovery platform). This carrier slows renal clearance and proteolysis, giving the molecule a terminal half-life of roughly 5 days (approximately 100-115 hours in healthy and hepatically impaired subjects, with some first-in-human data reporting up to ~7 days) and supporting fixed once-weekly subcutaneous dosing [7]. After a subcutaneous injection it is absorbed slowly, reaching peak plasma concentrations at about 4-6 days, and accumulates roughly 3-4-fold to steady state over repeated weekly doses [7].\n\nPharmacologically it activates two complementary receptors. The GLP-1 receptor arm acts on hypothalamic appetite centers and the gut to reduce food intake, slow gastric emptying, and enhance glucose-dependent insulin secretion. The glucagon receptor arm acts mainly on hepatocytes and adipose tissue to increase resting energy expenditure and upregulate hepatic beta-oxidation of fatty acids, accelerating clearance of intrahepatic triglyceride [1][8]. Because activating glucagon also tends to raise hepatic glucose output, the GLP-1 component must be balanced to offset it; efinopegdutide is tuned toward a relatively strong glucagon contribution, which is why its standout effect is on liver fat rather than on glycemia [1][8].\n\nThe injection is delivered subcutaneously into the abdomen, thigh or upper arm. In the liver-disease program the dose was titrated to a 10 mg weekly target over 8 weeks to limit gastrointestinal side effects, while the obesity and type 2 diabetes dose-ranging studies used fixed 5, 7.4 and 10 mg weekly doses without escalation [1][2][3].\n\nDownstream effects are dominated by hepatic and weight outcomes. In the Phase 2a NAFLD trial, 10 mg weekly produced a 72.7% relative reduction in liver fat content at 24 weeks, far exceeding semaglutide 1 mg (42.3%), with the majority of efinopegdutide patients reaching a normal (<5%) liver-fat fraction [1]. In obesity, the 10 mg dose drove 11.8% mean body-weight loss over 26 weeks, outperforming liraglutide 3 mg [2]. In type 2 diabetes, weight fell by up to roughly 8% but HbA1c did not improve, reflecting the glucose-raising pull of the glucagon arm [3]. Efinopegdutide originated at Hanmi (HM12525A), was licensed to Janssen (JNJ-64565111), and is now developed by Merck (MK-6024) under Fast Track designation for NASH; it remains investigational and is presented here for educational purposes only [5][6].
Clinical Trial Efficacy Highlights
- starRomero-Gómez and colleagues (J Hepatol 2023; the MK-6024 P001 Phase 2a study of 145 NAFLD patients) randomized participants to efinopegdutide 10 mg or semaglutide 1 mg subcutaneously once weekly, both titrated over 8 weeks. At Week 24 the least-squares mean relative reduction in liver fat content was 72.7% (90% CI 66.8-78.7) with efinopegdutide versus 42.3% (90% CI 36.5-48.1) with semaglutide (p<0.001), establishing superior liver-fat clearance for the dual co-agonist [1].
- starIn the same Phase 2a NAFLD study, body weight fell by 8.5% with efinopegdutide versus 7.1% with semaglutide at Week 24 (p=0.085, not statistically different), indicating that the larger liver-fat effect was not simply a function of greater weight loss and points to a direct hepatic glucagon-receptor mechanism [1][8].
- starAlba and colleagues (Clin Obes 2021) ran a 26-week Phase 2 dose-ranging trial in 474 adults with obesity without diabetes (mean BMI ~40.5). Least-squares mean body-weight change was −8.5% (5 mg), −9.8% (7.4 mg) and −11.8% (10 mg) versus −1.8% with placebo and −7.5% with liraglutide 3 mg; the 7.4 mg and 10 mg doses were statistically superior to liraglutide [2].
- starDi Prospero and colleagues (Clin Obes 2021) studied efinopegdutide in adults with type 2 diabetes and obesity. Placebo-subtracted body-weight reductions at Week 12 reached −4.56%, −5.85% and −7.23% for the 5, 7.4 and 10 mg doses (p<0.001), but HbA1c was not meaningfully improved, illustrating that the glucagon component can blunt glycemic benefit even as it amplifies weight and liver-fat effects [3].
- starAcross the obesity and diabetes programs, weight loss was dose-dependent and accompanied by reductions in waist circumference and fasting lipids, consistent with the energy-expenditure and hepatic lipid-oxidation actions described for GLP-1/glucagon co-agonists in mechanistic reviews [2][3][8].
- starPharmacokinetic data from the hepatic-impairment program (MK-6024-014) reported an apparent terminal half-life of approximately 115 hours in healthy subjects (extending to ~146-149 hours in moderate-to-severe hepatic impairment) with a Cmax near 0.47 µg/mL, supporting fixed once-weekly subcutaneous dosing without dose adjustment for liver impairment in the doses studied [7].
- starOn the strength of the Phase 2a liver-fat results, the FDA granted efinopegdutide Fast Track designation for NASH in June 2023, and Merck advanced the compound into Phase 2b development; there are no approved NASH/MASH co-agonist therapies, underscoring the unmet need the program targets [5][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 dominant and dose-related adverse events: nausea, vomiting, diarrhea and decreased appetite. Overall GI adverse-event rates ranged from about 71% at lower doses up to ~84% at the 10 mg dose, versus ~28% with placebo and ~60% with liraglutide, and were concentrated during titration [2].
- warningBecause the glucagon-receptor arm can raise hepatic glucose output, efinopegdutide did not improve HbA1c in type 2 diabetes and could transiently raise blood glucose; people with diabetes should have glucose monitored and not assume a glycemic benefit [3].
- warningLike other incretin agents, it can modestly increase resting heart rate and cause early satiety; dehydration from vomiting or diarrhea can occur, raising a theoretical risk of acute kidney injury if fluid intake is not maintained.
- warningInjection-site reactions (redness, itching, nodules) can occur with subcutaneous dosing; rotating sites between the abdomen, thigh and upper arm reduces local irritation.
- warningAs a GLP-1 receptor agonist class effect, it carries the standard cautions around pancreatitis and gallbladder events; the GLP-1 class label warning regarding thyroid C-cell tumors means it should be avoided in anyone with a personal or family history of medullary thyroid carcinoma or MEN2.
- warningGlucagon-driven energy expenditure may contribute to lean-mass loss if not balanced by adequate protein intake and resistance training, a general consideration for high-efficacy weight-loss agents [8].
- warningEfinopegdutide has not been studied in pregnancy or lactation and should be avoided in those settings; long-term cardiovascular and safety outcomes are not established because development is still at the Phase 2/2b stage.
- warningRegulatory/research status: efinopegdutide is NOT approved by the FDA, EMA or any regulator. It is an investigational drug available for research use only; this page is educational and not medical advice [5][6].
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 Efinopegdutide dosage?expand_more
In published clinical trials the typical Efinopegdutide dosage is 5, 7.4 or 10 mg subcutaneously once weekly, with 10 mg the target maintenance dose. In the NAFLD liver-disease program the dose was titrated up to 10 mg over an 8-week period to limit gastrointestinal side effects, whereas the obesity and type 2 diabetes dose-ranging studies used fixed 5, 7.4 or 10 mg weekly doses without escalation. The 10 mg weekly dose delivered the largest liver-fat reduction (72.7% at 24 weeks) and the greatest weight loss (11.8% over 26 weeks). These figures are an educational reference, not a prescription.
Is Efinopegdutide FDA approved?expand_more
No. Efinopegdutide (MK-6024, formerly JNJ-64565111 / HM12525A) is not approved by the FDA, the EMA or any other regulator for any indication. It is an investigational GLP-1/glucagon dual co-agonist that had completed Phase 2a/2 studies and received FDA Fast Track designation for NASH in 2023, with Phase 2b development underway. Because it is not approved, it is available only for research use, and the protocol on this page is educational content, not medical advice.
What is the half-life of Efinopegdutide?expand_more
Efinopegdutide has a long terminal half-life of roughly 5 days (approximately 100-115 hours in healthy and hepatically impaired subjects, with some first-in-human data reporting up to about 7 days). This is achieved by conjugating the peptide to an immunoglobulin-Fc carrier that slows clearance. After a subcutaneous dose it is absorbed slowly, peaking at about 4-6 days, and accumulates roughly 3-4-fold to steady state over repeated weekly injections, which is why fixed once-weekly dosing is sufficient.
How is Efinopegdutide reconstituted and administered?expand_more
In trials efinopegdutide was given as a once-weekly subcutaneous injection, so the reconstitution model here reflects its real route. For the educational protocol on this site, a 20 mg vial is mixed with 2.0 mL of bacteriostatic water to give 10 mg/mL. Draw the water slowly down the vial wall, swirl gently until clear, and refrigerate. At that concentration 5 mg ≈ 50 units, 7.4 mg ≈ 74 units, and 10 mg ≈ 100 units on a U-100 insulin syringe (one full syringe). Inject subcutaneously into the abdomen, thigh or upper arm, rotating sites, and discard the vial 28 days after reconstitution.
Can Efinopegdutide be stacked with other GLP-1 drugs like semaglutide or tirzepatide?expand_more
No. Efinopegdutide should not be combined with semaglutide, tirzepatide, liraglutide or any other GLP-1 or incretin agent. They act on overlapping receptors, so stacking sharply increases gastrointestinal toxicity, dehydration and pancreatitis risk without proven added benefit. Efinopegdutide also carries a glucagon-receptor component that can raise blood glucose, so combining it with other metabolic agents complicates glycemic control. It is an investigational compound with no validated combination protocol; any use should be supervised by a qualified clinician.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Efinopegdutide, plus the universal dosing calculator.
Academic References & Study Citations
Romero-Gómez M, Lawitz E, Shankar RR, et al; MK-6024 P001 Study Group. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. J Hepatol. 2023;79(4):888-897. View Scientific Paper →
Alba M, Yee J, Frustaci ME, Samtani MN, Fleck P. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study. Clin Obes. 2021;11(2):e12432. View Scientific Paper →
Di Prospero NA, Yee J, Frustaci ME, Samtani MN, Alba M, Fleck P. Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose-ranging study. Clin Obes. 2021;11(2):e12433. View Scientific Paper →
ClinicalTrials.gov. A Study of Efinopegdutide (MK-6024) in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) (MK-6024-001). NCT04944992. View Scientific Paper →
Healio Gastroenterology. FDA grants fast track designation to Merck's efinopegdutide for treatment of NASH. June 15, 2023. View Scientific Paper →
Merck & Co. Merck to Present Data for Efinopegdutide (MK-6024), an Investigational GLP-1/Glucagon Receptor Co-agonist, in Patients with Nonalcoholic Fatty Liver Disease (NAFLD) at EASL 2023. Press release, June 12, 2023. View Scientific Paper →
ClinicalTrials.gov. A Study of Efinopegdutide in Participants With Hepatic Impairment (MK-6024-014). NCT06052566 (pharmacokinetics / terminal half-life data). View Scientific Paper →
Hope DCD, Vincent ML, Tan TMM. Striking the Balance: GLP-1/Glucagon Co-Agonism as a Treatment Strategy for Obesity. Front Endocrinol (Lausanne). 2021;12:735019. View Scientific Paper →