Ibutamoren, best known by its Merck code MK-677 (also MK-0677, L-163,191 and, more recently, LUM-201), is an orally active small molecule that makes the pituitary gland release more growth hormone (GH). It does this by mimicking ghrelin, the “hunger hormone,” at the ghrelin receptor. Merck and academic investigators tested it in clinical trials in the 1990s and 2000s for frailty in older adults, hip fracture recovery, osteoporosis, obesity and Alzheimer’s disease.

The most important fact: ibutamoren has never been approved as a medicine in the US. Trials showed that it reliably raises GH and insulin-like growth factor 1 (IGF-1) and adds about 1 kg of lean mass in older adults. They did not show gains in strength or function, and they found consistent rises in blood sugar. A hip fracture trial was stopped early because of a congestive heart failure signal. Today it is sold mostly online as a “research chemical” or supplement, and FDA lists it as a substance that raises significant safety risks in compounding.

This page summarizes what the clinical trials and FDA’s 2024 review report. It is for education only and is not medical advice.

Property	Detail
Drug class	Non-peptide growth hormone secretagogue; ghrelin receptor (GHSR) agonist
Other names	MK-677, MK-0677, L-163,191, LUM-201; usually supplied as ibutamoren mesylate
Route	Oral (tablets or capsules)
Doses used in trials	2–50 mg once daily in adults (25 mg in most long trials); 0.2–0.8 mg/kg/day in children
Half-life	Not established in published human studies; described as long-acting, with effects over 24 h after one dose
Main effect	About 1.5–1.8× higher GH and IGF-1 in older adults over 12 months
FDA status	Not approved; Category 2 (significant safety risks) for compounding since 2022–2023
US controlled substance	Not on DEA’s controlled substances list
WADA status	Prohibited at all times (S2.2.4, growth hormone secretagogues)

What it is

Ibutamoren is a spiro-indoline-piperidine compound built around the amino acid 2-aminoisobutyric acid. The free base has the formula C₂₇H₃₆N₄O₅S and a molecular weight of 528.7 g/mol (PubChem CID 178024). The mesylate salt used in trials is C₂₈H₄₀N₄O₈S₂, 624.8 g/mol (PubChem CID 6450830). Despite how it is often marketed, it is not a peptide and not a SARM (selective androgen receptor modulator). It does not act on the androgen receptor (FDA briefing document, 2024).

Merck chemists designed it in the early 1990s as an oral replacement for GH-releasing peptides such as GHRP-6, which barely survive oral dosing. In rat pituitary cells it released GH at very low concentrations (EC50 1.3 nM), and in dogs it raised GH after oral doses as low as 0.125 mg/kg without meaningful effects on aldosterone, LH, thyroxine or prolactin (Patchett et al., PNAS 1995).

How it raises growth hormone

Ibutamoren binds and activates the ghrelin receptor, a G-protein-coupled receptor found on GH-producing cells of the pituitary and on hypothalamic neurons. FDA’s review summarizes two routes (FDA briefing document, 2024):

direct stimulation of GH release from pituitary somatotrophs;
activation of hypothalamic neurons that release growth hormone-releasing hormone (GHRH), which in turn stimulates the pituitary.

Because it works through the body’s own pituitary, it amplifies the natural pulses of GH rather than replacing them. In older adults, 2 weeks of 25 mg/day roughly doubled (+97%) the mean 24-hour GH level by making existing pulses taller, without changing how many pulses occurred (Chapman et al., JCEM 1996). This is the main difference from injected growth hormone, which bypasses the pituitary. The ghrelin receptor also controls appetite, which explains why increased hunger is the most common side effect.

Pharmacokinetics

Very little human pharmacokinetic data have been published. In its 2024 review, FDA found only two statements in the literature: that MK-677 has “high oral bioavailability” and a “long duration of action,” and that a single dose is long-acting (24 hours). FDA did not identify any additional human PK data (FDA briefing document, 2024).

Parameter	What is reported	Basis
Oral bioavailability	Over 60%	Dogs (Patchett et al., PNAS 1995)
Duration of action	About 24 h after one dose; supports once-daily dosing	Human trials, as summarized by FDA
Plasma half-life	4.7 h listed in one review table, without a primary human study cited	Sigalos and Pastuszak, Sex Med Rev 2018
Metabolism	Oxidation (CYP450) and glucuronidation	Horse liver microsomes and horses, per FDA

The figure of “24 hours” often quoted online describes how long GH and IGF-1 stay raised after a dose, not a measured plasma half-life.

Tolerance is a real question. In rats, daily dosing for 6 weeks brought GH levels back to those of untreated animals (FDA briefing document, 2024). In humans the response was blunted but not lost. Peak GH after the first 25 mg dose was 55.9 µg/L and fell to 22.6 µg/L after a week of dosing (Murphy et al., JCEM 1998). Even so, in older adults the 24-hour mean GH was still 1.8 times baseline after 12 months (Nass et al., Ann Intern Med 2008).

Regulatory status

Ibutamoren is not a component of any FDA-approved drug and has no USP monograph (FDA briefing document, 2024). Key regulatory points:

Compounding. FDA placed ibutamoren mesylate in Category 2 of its bulk drug substance lists for outsourcing facilities on December 29, 2022 and for pharmacies on September 29, 2023. FDA’s stated reason is “the potential for congestive heart failure in certain patients” (FDA Category 2 list).
Advisory committee. On October 29, 2024, FDA’s Pharmacy Compounding Advisory Committee voted 13 to 1 against adding ibutamoren mesylate to the 503A bulks list. Members cited weak evidence of efficacy and concerns about fluid retention, heart failure and high blood sugar (PCAC minutes, 2024).
Pediatric development. Lumos Pharma studied it as LUM-201, an oral treatment for children with growth hormone deficiency (Bright and Thorner, Horm Res Paediatr 2022). It has not been approved for this use.
Controlled substances. It does not appear on DEA’s list of controlled substances (DEA).
Sport. WADA names ibutamoren (MK-677) as an example of a growth hormone secretagogue under S2.2.4. It is prohibited in and out of competition and is a non-specified substance (WADA Prohibited List 2026).

What the research shows

Merck and academic groups ran several randomized, placebo-controlled trials. Almost all used 25 mg once daily. The consistent pattern: IGF-1 rises by about 40–85%, lean mass rises modestly, and clinical outcomes (strength, function, disease progression) do not improve.

Healthy older adults: body composition

The longest trial randomized healthy adults aged 60–81 to 25 mg/day or placebo for 12 months, followed by a 12-month extension. Results for the 65 analyzed participants (Nass et al., Ann Intern Med 2008; PMC full text):

Outcome at 12 months	Placebo	MK-677 25 mg	p
24-h mean GH	—	1.8× baseline	under 0.001
IGF-1	—	1.5× baseline	under 0.001
Fat-free mass	−0.5 kg (95% CI −1.1 to 0.2)	+1.1 kg (95% CI 0.7 to 1.5)	under 0.001
Body weight	+0.8 kg	+2.7 kg	0.003
Limb fat	+0.24 kg	+1.1 kg	0.001
Abdominal visceral fat	No difference	No difference	NS
Fasting glucose	0.0 mmol/L	+0.3 mmol/L (≈5 mg/dL)	0.015
HbA1c	−0.1 points	+0.2 points	0.002
Strength and physical function	No change	No change	NS

The gain in fat-free mass did not translate into strength or function, although the authors noted the study was not powered for those outcomes. LDL cholesterol fell slightly (−5.4 mg/dL) and cortisol rose (+1.7 µg/dL) on MK-677. Bone density changes were consistent with faster bone remodeling.

An earlier 4-week dose-ranging trial in 32 adults aged 64–81 found that 25 mg/day raised IGF-1 from 141 to 265 µg/L, into the range of young adults (Chapman et al., JCEM 1996).

Hip fracture recovery

Two trials tested whether raising GH would speed recovery in older adults after hip fracture:

Trial	Design	IGF-1 effect	Functional result
Bach et al., J Am Geriatr Soc 2004	161 patients aged 65 and older; 25 mg/day vs placebo for 6 months	+84% vs +17%	No significant difference on functional measures or the Sickness Impact Profile
Adunsky et al., Arch Gerontol Geriatr 2011	123 patients; 25 mg/day (n = 62) vs placebo (n = 61) for 24 weeks	+51.4 ng/mL vs placebo	Gait speed improved; stair-climbing power and most other measures did not

The second trial was stopped early because of a safety signal of congestive heart failure (see Side effects below).

Alzheimer’s disease

In animals, IGF-1 helps clear beta-amyloid from the brain. Merck tested this idea in 563 patients with mild to moderate Alzheimer’s disease, randomized to 25 mg/day or placebo for 12 months (Sevigny et al., Neurology 2008). IGF-1 rose 60.1% at 6 weeks and 72.9% at 12 months. However, there was no difference from placebo on any of the four measures of cognition, daily function or global change. The drug engaged its target but did not slow the disease.

Osteoporosis and bone

A trial in 292 postmenopausal women aged 64–85 with low hip bone density compared MK-677 25 mg, alendronate 10 mg, both, or placebo (Murphy et al., JCEM 2001):

MK-677 alone raised markers of both bone formation (osteocalcin +22%) and bone breakdown (urinary NTx +41%).
Combined with alendronate, it raised femoral neck bone density more than alendronate alone (4.2% vs 2.5%).
It gave no extra benefit at the lumbar spine, total hip or whole body.

The authors judged that the limited benefit was a concern when weighed against GH-related side effects.

Obesity and calorie restriction

Obese men. In 24 obese men aged 18–50, 25 mg/day for 8 weeks raised IGF-1 by about 40% and increased fat-free mass. Total and visceral fat did not change. Basal metabolic rate rose at 2 weeks but not at 8 weeks, and an oral glucose tolerance test showed worse glucose handling (Svensson et al., JCEM 1998).
Diet-induced muscle breakdown. In a crossover study, 8 healthy volunteers aged 24–39 ate a calorie-restricted diet. In the week they took 25 mg/day, nitrogen balance (a marker of whole-body protein breakdown) was +0.31 g/day, compared with −1.48 g/day on placebo (Murphy et al., JCEM 1998).

Sleep

A small crossover study gave MK-677 at bedtime to 8 young adults for 7 days and 6 older adults for 14 days (Copinschi et al., Neuroendocrinology 1997). In the young adults, 25 mg increased stage IV (deep) sleep by about 50% and REM sleep by more than 20% compared with placebo. In the older adults, REM sleep rose by nearly 50%. This has not been tested in larger or longer trials.

Children with growth hormone deficiency

A 6-month randomized trial included 68 prepubertal children with growth hormone deficiency. They received LUM-201 0.4 or 0.8 mg/kg/day, or placebo (Bright et al., J Endocr Soc 2021). As summarized by FDA, annualized height velocity was:

Group	Height velocity
Placebo	4.5 cm/year
LUM-201 0.4 mg/kg/day	6.0 cm/year
LUM-201 0.8 mg/kg/day	6.9 cm/year
Injected recombinant GH	11.1 cm/year

Children with some remaining pituitary function responded best: baseline IGF-1 over 30 ng/mL and a peak GH of at least 5 ng/mL after a test dose. Children with more severe deficiency did better on injected GH (FDA briefing document, 2024). The analysis used data collected in 1996–1998.

About “natural GH without side effects.” MK-677 is often marketed as a safe, oral way to get the benefits of growth hormone. The trials do not support this. It raised blood sugar and lowered insulin sensitivity in nearly every study. It caused fluid retention and joint and muscle pain, as injected GH does. And it was linked to heart failure in frail older patients. Its added lean mass also did not make people stronger in the trials that measured strength.

Side effects and risks

FDA’s 2024 review concluded there are “serious safety concerns” including high blood sugar, liver enzyme elevations, edema and fluid overload, and heart failure in older patients recovering from hip fracture (FDA briefing document, 2024).

Common effects

In the 12-month trial in healthy older adults, these were the most frequent effects (Nass et al., Ann Intern Med 2008; PMC full text):

Effect	Placebo	MK-677 25 mg
Increased appetite	36%	67% (p = 0.02)
Mild, transient leg swelling (edema)	27%	44%
Transient muscle pain	9%	33%
Joint pain	77%	58%

Increased appetite settled within 3 months in half the participants. Other trials reported headache, night sweats, bloating, abdominal discomfort and isolated cases of carpal tunnel syndrome. Prolactin rose by about 23–27% but generally stayed in the normal range (Chapman et al., JCEM 1996; FDA briefing document, 2024).

Blood sugar and insulin resistance

This is the most consistent adverse finding:

Older adults, 4 weeks. Fasting glucose rose from 5.4 to 6.8 mmol/L (≈97 to ≈122 mg/dL) on 25 mg/day (Chapman et al., JCEM 1996).
Older adults, 12 months. HbA1c rose 0.2 points. Eight participants had an HbA1c over 6% at 12 months, and insulin sensitivity fell (Nass et al., Ann Intern Med 2008).
Alzheimer’s trial. Blood glucose increases were reported in 15.4% on MK-677 vs 4.6% on placebo, and HbA1c increases in 11.1% vs 1.4% (FDA briefing document, 2024).
Functionally impaired older adults, 9 weeks. 6% needed a dose reduction for fasting glucose over 140 mg/dL, and three of them stopped because of high glucose despite the lower dose (FDA briefing document, 2024).

People with diabetes were excluded from the main trials, so the effect in people who already have it is unknown.

Heart failure and blood pressure

In the 2011 hip fracture trial, congestive heart failure occurred in 4 patients (6.5%) on MK-677 vs 1 (1.7%) on placebo, and the trial was stopped. Systolic blood pressure rose by 11.9–16.4 mmHg on MK-677, compared with changes of −2.3 to +2.3 mmHg on placebo. Serious adverse events occurred in 24% vs 13% of patients (Adunsky et al., Arch Gerontol Geriatr 2011; FDA briefing document, 2024). This finding is the basis for FDA’s Category 2 listing.

Liver enzymes

Reversible rises in liver enzymes (transaminases) appeared in several trials. In one, 2 of 30 older adults had levels 1.5–2.5 times the upper limit of normal. In the osteoporosis trial, 2 women on MK-677 alone stopped because of levels more than 3 times the upper limit (FDA briefing document, 2024). A 2025 case report described a healthy man in his early 30s who developed raised liver enzymes (transaminitis) after 2 months of MK-677 bought as a supplement. His liver tests returned to normal after he stopped (Cobani et al., BMJ Case Rep 2025).

Cancer and long-term IGF-1 exposure

No long-term cancer data exist for ibutamoren, and FDA found no animal carcinogenicity studies. In the 2-year older-adult trial, one woman on MK-677 was diagnosed with adenocarcinoma of the tongue and one had a heart attack 7 days after starting. One placebo recipient developed kidney cancer. The trial was too small to judge whether these were related to treatment (Nass et al., Ann Intern Med 2008). Because ibutamoren raises GH and IGF-1, FDA considers that the warnings on approved GH products may also apply. These include new tumors (neoplasms), glucose intolerance, fluid retention and intracranial hypertension (FDA briefing document, 2024).

Use with SARMs

Ibutamoren is often taken together with SARMs. A case report followed a 25-year-old man who took ligandrol (LGD-4033) 10 mg and MK-677 15 mg daily for 5 weeks (Cardaci et al., Exp Physiol 2022). Results:

HDL cholesterol fell 36%.
ALT rose 205%.
Total testosterone fell 62%.
Bone mineral density fell 2.1%.

Most values recovered after stopping. The effects of the two compounds cannot be separated in a single case.

Who was excluded or at higher risk

The trials excluded people with diabetes, cancer (other than some skin cancers), uncontrolled hypertension and congestive heart failure (Bach et al., J Am Geriatr Soc 2004; Nass et al., Ann Intern Med 2008). No human data exist for pregnancy. In mice, both activating and blocking the ghrelin receptor harmed fertilization and fetal development, which FDA flagged as a possible class effect (FDA briefing document, 2024).

Quality and contamination

Products sold online are not made under drug manufacturing standards. FDA noted that the certificates of analysis submitted with nominations had no data on chiral purity, impurities or residual solvents (FDA briefing document, 2024). One consumer report to FDA described capsules labeled “Not for Human Consumption, For Laboratory Use Only.”

A 5-year surveillance study by European and other official medicines control laboratories analyzed 324 samples of SARMs, metabolic modulators and secretagogues from 13 countries, mostly from illegal distribution (Barrios et al., Drug Test Anal 2025):

ibutamoren was first among the five most frequently reported molecules;
24% of products were sold as dietary supplements;
some products were overdosed.

Key takeaways

An oral ghrelin mimic, not a peptide or SARM. Ibutamoren activates the ghrelin receptor to amplify the body’s own GH pulses. At 25 mg/day it raised IGF-1 by about 40–85% across trials.
Small lean-mass gains, no functional benefit. Older adults gained about 1.1 kg of fat-free mass over a year, but strength and function did not improve. Hip fracture and Alzheimer’s trials missed their clinical goals.
Blood sugar rises consistently. Fasting glucose, HbA1c and insulin resistance rose in nearly every trial, and some participants needed dose reductions.
Heart failure signal in frail patients. A hip fracture trial stopped early after more heart failure cases on the drug. This underlies FDA’s Category 2 compounding listing.
Unapproved, prohibited in sport, poorly characterized. No human pharmacokinetic study has been published in detail. WADA bans it at all times, and products sold online have uncertain contents.

Sources

Patchett AA, Nargund RP, Tata JR, et al. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc Natl Acad Sci U S A. 1995;92(15):7001–7005. PubMed.
Chapman IM, Bach MA, Van Cauter E, et al. Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab. 1996;81(12):4249–4257. PubMed.
Copinschi G, Leproult R, Van Onderbergen A, et al. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology. 1997;66(4):278–286. PubMed.
Murphy MG, Plunkett LM, Gertz BJ, et al. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 1998;83(2):320–325. PubMed.
Svensson J, Lönn L, Jansson JO, et al. Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab. 1998;83(2):362–369. PubMed.
Murphy MG, Weiss S, McClung M, et al. Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab. 2001;86(3):1116–1125. PubMed.
Bach MA, Rockwood K, Zetterberg C, et al. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. 2004;52(4):516–523. PubMed.
Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008;149(9):601–611. PubMed; PMC.
Sevigny JJ, Ryan JM, van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. 2008;71(21):1702–1708. PubMed.
Adunsky A, Chandler J, Heyden N, et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011;53(2):183–189. PubMed.
Bright GM, Do MT, McKew JC, et al. Development of a predictive enrichment marker for the oral GH secretagogue LUM-201 in pediatric growth hormone deficiency. J Endocr Soc. 2021;5(6):bvab030. PubMed.
Bright GM, Thorner MO. A GH secretagogue receptor agonist (LUM-201) elicits greater GH responses than standard GH secretagogues in subjects of a pediatric GH deficiency trial. Horm Res Paediatr. 2022;95(1):76–81. PubMed.
Sigalos JT, Pastuszak AW. The safety and efficacy of growth hormone secretagogues. Sex Med Rev. 2018;6(1):45–53. PubMed.
Food and Drug Administration. FDA briefing document: Pharmacy Compounding Advisory Committee meeting, October 29, 2024 (evaluation of ibutamoren mesylate for inclusion on the 503A bulk drug substances list). FDA.
Food and Drug Administration. Final summary minutes of the Pharmacy Compounding Advisory Committee meeting, October 29, 2024. FDA.
Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks (Category 2). FDA.
World Anti-Doping Agency. The 2026 Prohibited List, in effect January 1, 2026. WADA.
Drug Enforcement Administration, Diversion Control Division. Controlled substances, alphabetical order. DEA.
National Center for Biotechnology Information. Ibutamoren, PubChem CID 178024; ibutamoren mesylate, PubChem CID 6450830. PubChem; PubChem.
Cobani E, Amin MS, Hasso M, Kumbar L. Hepatotoxicity induced by MK-677. BMJ Case Rep. 2025;18(7):e265728. PubMed.
Cardaci TD, Machek SB, Wilburn DT, et al. LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: a case report. Exp Physiol. 2022;107(12):1467–1476. PubMed.
Barrios MM, Deconinck E, Vanhee C, et al. SARMs, metabolic modulators and growth hormone secretagogues in suspected illegal medicines, bought as sport performance enhancers: a retro- and prospective study within the GEON. Drug Test Anal. 2025;17(10):2078–2085. PubMed.

Ibutamoren (MK-677)