HM15136
A weekly glucagon analogue built to raise blood sugar in a rare disease where insulin will not stop coming
Glucagon is the body's answer to low blood sugar, but it lasts minutes and barely dissolves. HM15136, also called efpegerglucagon, is glucagon fused to an antibody fragment so it lasts days. It is being developed for congenital hyperinsulinism, and its published human record is three studies long.
What is it?
Congenital hyperinsulinism is the mirror image of diabetes: the pancreas keeps releasing insulin whatever the blood sugar does, and the resulting hypoglycaemia can damage a developing brain. One drug is approved for it, and up to 60% of patients do not respond. Glucagon would be the obvious counterweight, but it is cleared in minutes and is barely soluble.
HM15136 answers both problems at once. Conjugating a glucagon analogue to an IgG4 Fc fragment through a polyethylene glycol linker raised its solubility from 0.03 to at least 150 mg/mL and its half-life in mice from under five minutes to 36 hours. In rats and mice with hyperinsulinism it reversed insulin-induced hypoglycaemia and held glucose up across repeated doses.
In people the picture is early but coherent. Fifty-six healthy adults took a single dose of 10 to 120 µg/kg: all adverse events were mild, fasting glucose rose at 50 µg/kg and above, and the body's own glucagon was suppressed for over two weeks. In overweight and obese patients, twelve weeks of weekly dosing raised fasting glucose and produced modest weight loss.
The only published treatment account is a single patient: a 29-year-old woman whose hyperinsulinism came from a glucokinase variant and who kept having hypoglycaemia despite standard care. She entered the phase 2 trial, continued through expanded access, and had better glucose control across ten months.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Half-Life: How Much Remains
The dataset records a half-life of 77 to 101 hours (terminal) for HM15136. After each half-life, half of what was in the circulation is gone, so about 3% remains after five. Real clearance varies with the person, the dose, the route and kidney or liver function; this is arithmetic on a published figure, not a dosing tool.
Published Research
These are the studies that describe HM15136, read from their PubMed abstracts: two early-phase trials in people and the rodent study behind them.
First in humans
Fifty-six adults took a single injection of 10 to 120 µg/kg or placebo. Every adverse event was mild and transient; nausea occurred only at the top two doses. From 50 µg/kg upwards fasting glucose rose, peaking at day 10, while the body's own glucagon stayed suppressed to day 17.
Twelve weeks of weekly dosing
Overweight and obese patients with dyslipidaemia or hypertension, with and without type 2 diabetes, took 0.02, 0.04 or 0.06 mg/kg weekly for twelve weeks. Fasting glucose rose with dose, as the mechanism predicts, and weight fell 0.5%, 2.3% and 2.6%. Antibodies appeared in five of 27.
Why the molecule is built this way
Conjugating a glucagon analogue to an IgG4 Fc fragment raised solubility from 0.03 to at least 150 mg/mL and the half-life in mice from under five minutes to 36 hours, with 90% bioavailability. It reversed insulin-induced hypoglycaemia and held glucose up in rats with hyperinsulinism.
Side Effects & Contraindications
Reported Side Effects
From the two early-phase trials; there is no approved label.
Contraindications & Cautions
An investigational drug for a rare disease, available only through trials and expanded access.
Legal Status
HM15136 is investigational everywhere.
Frequently Asked Questions
?What is HM15136?
A long-acting glucagon analogue, also called efpegerglucagon, made by fusing glucagon to an IgG4 antibody fragment so a single injection lasts about a week.
?What is it for?
Congenital hyperinsulinism, a rare disease in which the pancreas keeps making insulin and blood sugar falls dangerously; few patients respond well to the one approved drug.
?Is it a weight-loss drug?
No. It is given to raise blood sugar, and the weight changes in its trial were small.
?How far along is it?
Early. Two published early-phase trials, a rodent study and one patient treated for ten months through expanded access.
References
- [pubmed] Huh KY, et al. "A double-blind, placebo-controlled, single-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM15136, a novel long-acting glucagon analogue, in healthy subjects." Diabetes Obes Metab, 2022;24(3):411-420. PMID: 34726329.
- [pubmed] Shin W, et al. "Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities." Diabetes Obes Metab, 2023;25(9):2723-2733. PMID: 37311732.
- [pubmed] Heo YH, et al. "A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism." Sci Rep, 2022;12(1):16765. PMID: 36202918.
- [pubmed] Cannon M, et al. "Treatment of Congenital Hyperinsulinism With a Novel, Long-acting Glucagon Analogue." JCEM Case Rep, 2025;3(11):luaf235. PMID: 41080976.
- [other] US FDA, Drugs@FDA (openFDA): no application for HM15136 or efpegerglucagon. Read September 30, 2026.
- [clinicaltrials] ClinicalTrials.gov NCT04732416: phase 2 trial of HM15136 (efpegerglucagon) in congenital hyperinsulinism, ages 2 and over (registry read September 30, 2026).
Sources & Citations
Studies were read from PubMed; regulatory sources are listed below, read September 30, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.