LEAP2_Dosage, benefits & legal status
Also known as LEAP-2, liver-expressed antimicrobial peptide 2
The natural brake on the receptor that ghrelin and the GHRP peptides switch on. Two small infusion studies in men found about 12% less food eaten at one meal, and no drug program exists.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is LEAP2?
Plain language first. The technical label stays, but it never stands alone.Overview
The body makes its own brake on hunger signaling: LEAP2, released by the liver, blocks the ghrelin receptor that the hunger hormone ghrelin and peptides such as ipamorelin and GHRP-6 switch on. Infused into a vein for one day, it cut food eaten at a buffet meal by about 12% in 20 lean men (432 kJ less) and in 20 men with obesity (411 kJ less), and blood sugar rose less after a meal. The lean men ate less without rating themselves less hungry, and only these 40 men have received it: no women, no repeat dosing, no weight outcome and no drug program.
LEAP2 is a 40-residue peptide with two disulfide bonds, released by the liver and small intestine, that acts at the ghrelin receptor (GHS-R1a) as both an antagonist and an inverse agonist: it blocks acyl ghrelin and also damps the receptor's baseline signaling. Ge and colleagues reported the antagonism in Cell Metabolism 2018 and described it as noncompetitive; the inverse agonism was shown later, by M'Kadmi and colleagues in the Journal of Medicinal Chemistry 2019. Its blood level runs higher in obesity, the opposite of ghrelin, whose level runs lower. The rise after a meal is clear in mice; in men, Hagemann and colleagues found no rise after a meal. Two randomized, double-blind, placebo-controlled crossover infusion studies of 20 men each confirmed the mechanism in people: growth hormone fell, food intake at one meal fell about 12% and blood glucose rose less after a meal.
What it's used for
Nothing outside research. It is sold only as a laboratory reagent and has been given to people only as a one-day infusion in two small studies of appetite and blood sugar.
How does LEAP2 work?
What it does in the body, and where.LEAP2 is a natural brake on the ghrelin receptor, the switch that ghrelin and the GHRP peptides turn on.
- 01Released after mealsThe liver and small intestine release LEAP2 into the blood. Its level runs higher in obesity, while ghrelin runs lower. In mice it also rises after a meal, but in men Hagemann and colleagues found no rise after a meal. The balance between the two, rather than either alone, is the proposed signal.
- 02Blocking and quieting the receptorLEAP2 binds the growth hormone secretagogue receptor (GHS-R1a), the same receptor that ghrelin, ipamorelin, GHRP-2, GHRP-6, hexarelin, MK-677, anamorelin, macimorelin and relamorelin switch on. It keeps acyl ghrelin from activating the receptor and also turns down the receptor's own baseline activity. Most of the body's peptides switch their receptors on; LEAP2 holds this one down.
- 03What changed in peopleIn both human studies growth hormone fell, the clearest sign the receptor was blocked, and the men ate about 12% less at the next meal. Blood ghrelin itself did not change, so the effect is at the receptor. Glucose rose less after meals. Glucagon rose in the lean men, and stomach emptying slowed in the men with obesity but not in the lean men, where the paracetamol marker showed no difference; in mice lacking the receptor, LEAP2 had no effect on food intake or glucose.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
First infusion in people (lean men)
Early research- Human trial20 healthy lean men, randomized double-blind crossover: 25 pmol/kg/min cut buffet intake by 12% (432 kJ, 95% CI 155 to 709; P=0.0041) and shortened the meal by 1.5 minutes (P=0.0303).
- No dataRatings of hunger, satiety, fullness and nausea did not differ from placebo: the men ate less without feeling less hungry.
- Human trialPeak glucose 6.21 against 6.58 mmol/L (P=0.005); growth hormone area under the curve 33.8 against 106 ng/mL×min (P=0.001); acyl ghrelin unchanged (P=0.634).
Men with obesity
Early research- Human trial20 men with obesity, randomized double-blind crossover: 40 pmol/kg/min for 320 minutes raised blood LEAP2 about fivefold and cut buffet intake by about 12% (411 kJ, P=0.015).
- Human trialPeak glucose 6.6 against 7.0 mmol/L and glucose area after the meal 1,125.0 against 1,176.0 mmol/L×min (both P<0.001); insulin and C-peptide rose, growth hormone fell and stomach emptying slowed.
- No dataA small, single-day study; these figures come from a secondary summary of the paper.
Proof of the receptor in mice
Research only- Animal studyLEAP2 reduced food intake and glucose in normal mice but not in mice lacking the ghrelin receptor; the mature peptide is identical in mice and humans.
Discovery as a ghrelin receptor blocker
Research only- Lab studyIdentified as an endogenous antagonist of the ghrelin receptor. The authors described the antagonism as noncompetitive. The inverse agonism, suppression of the receptor's baseline activity, was shown by other groups in 2019.
LEAP2 is often described as preclinical, with only observational human data; it has been infused into 40 men in two randomized, double-blind, placebo-controlled crossover studies with published food-intake and glucose results, though no drug program exists. A human study dated August 14, 2024, is reported to have linked blood LEAP2 levels to metabolic traits; no such paper could be found, and the 2024 human paper from this field (Englund and colleagues, Peptides, April 22, 2024) measured where LEAP2, ghrelin and their receptor are made in the gut and liver, without giving anyone LEAP2. It is reported to reduce hunger in people, but in lean men food intake fell 12% with no change on any rating of hunger, fullness or nausea. It is also framed as a weight-loss peptide: neither human study measured weight, both covered a single day and one meal, and the weight loss was in mice, given a long-acting analog rather than LEAP2 itself. The men with obesity received a 60% higher infusion rate (40 against 25 pmol/kg/min) for a similar effect (411 against 432 kJ), so the two studies do not show a dose response. LEAP2 (38-77) and LEAP2 1-40 name the same 40-residue peptide (numbered 37-76 in mice), while short pieces such as LEAP-2 (1-10) amide are research tools, not the natural peptide. The name says antimicrobial, but no antimicrobial use exists and its potency against bacteria has not been established; current interest is metabolic.
The published record
Papers and trials about LEAP2
136 papers tagged human · 101 not reviews or lab · 15 clinical trial publications
9 registered trials · none with posted results
Furthest stage reached: Phase 1, completed, no results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about LEAP2
Evidence
Category
Weight loss and metabolic
Common vial
Varies
Half-life
About 9 minutes
How much, and do you cycle it?
The range, and whether you take breaks.25 or 40 pmol/kg/min as a continuous infusion (two human studies), once, as a one-day infusion (studies). No schedule exists; each person received one infusion on a single day Human study
Each man received LEAP2 on one study day and placebo on another, and 8 of the lean men had one further infusion day for the kinetics sub-study. No study has tested repeat doses, longer use or breaks.
About 9 minutesHuman study
A kinetics sub-study in 8 of the 20 lean men gave a plasma half-life of about 9 minutes (9.1, standard deviation 2.5), a metabolic clearance rate of 0.86 L/min (standard deviation 0.17) and a volume of distribution of 14 L (standard deviation 5.3). Those 8 men received 101 pmol/kg/min for 10 minutes and then 25 pmol/kg/min for 110 minutes. In the main study 25 pmol/kg/min held blood LEAP2 at 41.2 ng/mL from about 45 minutes on, about 2.6 times the placebo level, and 40 pmol/kg/min in men with obesity raised it about fivefold. There is no bioavailability figure for any route other than a vein.
Source: Hagemann CA et al., Cell Reports Medicine 2022;3:100582 (kinetics sub-study in 8 men)
You can compare this against the whole library to see where it sits.
How is it given?
Dosing context and source notes.Given in hospital from a prepared product, so there is nothing to mix.
Both human studies gave it as a continuous infusion into a vein on a single day: 25 pmol/kg/min (115 ng/kg/min) in 20 healthy lean men, from the start of the study day until they had eaten a buffet meal served at 260 minutes, and 40 pmol/kg/min for 320 minutes in 20 men with obesity, raising blood LEAP2 about fivefold. The lean-men study used the natural 40-residue form at more than 98% purity. There is no form for use under the skin or by mouth, and no kidney or liver dose data, and laboratory suppliers sell it only as a research reagent. These are rates for a research infusion, not a treatment dose, so the calculator starts with an empty dose field.
How do you store it?
Before mixing, and after.Given in a hospital or trial clinic, so the pharmacy stores it.
LEAP2 goes into a vein and is prepared by hospital, clinic or trial pharmacy staff, following the product label or the trial protocol. Some products like this are ready-made solutions and others are powders mixed just before use, often with hours rather than weeks of shelf life once prepared. It is not a medicine people store at home.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 35% charged residues, 45% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Not studied in women: both human studies enrolled men only
- Not studied in pregnancy or breastfeeding: no data exist
- Not studied beyond a single day, or as repeated doses
- Not studied in people with diabetes: both studies enrolled otherwise healthy men
- Not studied under the skin or by mouth, or in kidney or liver disease: both studies infused it into a vein
Stop and get help
- Any new or unexpected symptom during an infusion: only 40 men have received it, so its side effects are not established
Common effects
- No adverse events reported during infusions in 20 lean men; nausea and comfort ratings matched placebo
- Growth hormone suppressed: area under the curve 33.8 against 106 ng/mL×min on placebo (P=0.001) in lean men, and lower throughout the infusion in men with obesity
- Glucagon about 2 pmol/L higher both fasting and after the meal (postprandial P<0.001, fasting P=0.038) and fasting insulin higher (2.39 against 1.92 nmol/L×min, P<0.001) in lean men
- Slower stomach emptying in men with obesity
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is LEAP2 approved?
And where the numbers on this page come from.No. LEAP2 is not approved for any use, anywhere. It is sold labeled for laboratory research only, and there is no legal route to buy it for human use.
- Approval statusResearch only
- RouteInto a vein (in studies)
- Checked21 October 2026
- DoseFrom published human studies. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesUniProt Q969E1, liver-expressed antimicrobial peptide 2FDA GSRS substance record, liver-expressed antimicrobial peptide 2 (UNII A4E5SCW9Z5)Ge X et al., Cell Metabolism 2018;27:461-469.e6Hagemann CA et al., Cell Reports Medicine 2022;3:100582OpenAlex record, Hagemann CA et al. 2022Englund A et al., Diabetes 2026;75:925-937MD Newsline, summary of Englund A et al., Diabetes 2026Englund A et al., Peptides 2024;177:171227Google Patents, US10781253B2, LEAP2 binding agents and compositions thereof
What has happened recently
Not approved anywhere and not in development as a drug: it has no INN, no company development program and no designation that could be found, although both human studies were registered as early phase 1 by their academic sponsor. LEAP2 was named as an antimicrobial peptide made in the liver; Ge and colleagues identified it as the body's own ghrelin receptor antagonist in Cell Metabolism, online in December 2017 and in the February 2018 issue. All human work comes from academic groups in Copenhagen led by Filip Krag Knop, with Birgitte Holst on the first study: Hagemann and colleagues published the first infusion study on March 30, 2022; the crossover study is NCT04621409 and NCT04897984 is the separate kinetics sub-study in 8 of the same men. Englund and colleagues published the study in men with obesity in Diabetes, dated March 30, 2026, registered as NCT05603598. Other work is preclinical, including a long-acting analog tested in mice, and US patent US10781253B2, granted to NGM Biopharmaceuticals in September 2020 and naming the discovery paper's senior author as an inventor, covers agents that bind LEAP2, the opposite approach; it is now listed as expired for unpaid fees. It is sold only as a laboratory reagent; its FDA UNII is A4E5SCW9Z5.
You can compare this against the whole library, or read how to check a seller.
What else is like LEAP2?
Others in Weight loss and metabolic, side by side.If you're weighing LEAP2, it's worth reading Semaglutide, Tirzepatide, and Retatrutide in the same class.
The natural brake on the receptor that ghrelin and the GHRP peptides switch on. Two small infusion studies in men found about 12% less food eaten at one meal, and no drug program exists.
- Dose
- 25 or 40 pmol/kg/min as a continuous infusion (two human studies)
- How often
- Once, as a one-day infusion (studies)
The drug in Ozempic and Wegovy: a weekly shot that curbs hunger for steady weight loss.
- Dose
- 0.25 up to 2.4 mg per week (start low, increase slowly)
- How often
- Weekly
The drug in Mounjaro and Zepbound: a weekly shot for major weight loss and blood sugar.
- Dose
- 2.5 up to 15 mg per week (start low, increase slowly)
- How often
- Weekly
An experimental weekly shot with some of the biggest weight-loss numbers yet in trials.
- Dose
- 1 up to 12 mg per dose (start low, increase slowly)
- How often
- Weekly
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- UniProt Q969E1, liver-expressed antimicrobial peptide 2(2026)77-residue precursor; mature chain at residues 38 to 77; disulfides Cys54 to Cys65 and Cys60 to Cys70; secreted; antimicrobial activity; NMR structure 2L1Q.
- FDA GSRS substance record, liver-expressed antimicrobial peptide 2 (UNII A4E5SCW9Z5)(2026)Registered as a protein under its descriptive name; no INN.
- Ge X et al., Cell Metabolism 2018;27:461-469.e6(2018)LEAP2 identified as an endogenous, noncompetitive antagonist of the ghrelin receptor; 16 authors, published online December 8, 2017; PMID 29233536.
- Hagemann CA et al., Cell Reports Medicine 2022;3:100582(2022)20 healthy lean men, randomized double-blind crossover, 25 pmol/kg/min: intake down 12% (432 kJ, P=0.0041), peak glucose 6.21 against 6.58 mmol/L, no change in appetite ratings, no adverse events; registered as NCT04621409 and NCT04897984.
- OpenAlex record, Hagemann CA et al. 2022(2022)13 authors, published March 30, 2022; PMID 35492241.
- Englund A et al., Diabetes 2026;75:925-937(2026)LEAP2 reduces ad libitum food intake and attenuates postprandial glucose excursions in men with obesity; 11 authors, Diabetes 2026;75(6):925-937, dated March 30, 2026; PMID 41911360. The abstract gives the rate as 40 pmol/kg/min over about 5 hours, a fivefold rise in plasma LEAP2 and food intake down about 12%, and reports no kJ figure.
- MD Newsline, summary of Englund A et al., Diabetes 2026(2026)Secondary summary: 20 men with obesity, 40 pmol/kg/min for 320 minutes; intake 411 kJ lower (P=0.015); peak glucose 6.6 against 7.0 mmol/L; growth hormone lower and stomach emptying slower.
- Englund A et al., Peptides 2024;177:171227(2024)Where LEAP2, ghrelin and their receptor are made along the human gut and in the liver (tissue expression study, no LEAP2 given); published April 22, 2024.
- Google Patents, US10781253B2, LEAP2 binding agents and compositions thereof(2020)Agents that bind LEAP2, including anti-LEAP2 antibodies, granted to NGM Biopharmaceuticals and now listed as expired for unpaid fees; neutralizing LEAP2 would raise ghrelin signaling rather than block it.
Beyond these, 403 records are indexed. Browse the records