# MK-677 (Ibutamoren) — Research Peptide Profile

> Research guide to MK-677 (ibutamoren) - an oral, non-peptide ghrelin receptor agonist studied for GH and IGF-1 elevation, body composition, and sleep.

Source: https://peptpedia.org/peptide/mk-677 | Published: 2026-07-18 | Last updated: 2026-07-18

## Overview

MK-677 (ibutamoren, L-163,191) is a spiropiperidine small molecule developed by Merck as an orally active ghrelin mimetic. It is not a peptide: unlike injectable growth hormone secretagogue peptides such as ipamorelin or GHRP-6, it survives oral dosing, and it is grouped with them only because it activates the same receptor, GHSR-1a. Clinical trials in healthy elderly subjects showed that 25 mg once daily restored GH and IGF-1 levels to the young-adult range, and a 2-year randomized trial in adults aged 60-81 found increased fat-free mass without measurable gains in strength or function. Development stopped short of regulatory approval; MK-677 has no approved indication anywhere and is prohibited in sport at all times under the WADA Prohibited List.

## Molecular Profile

- **Category:** growth-factors
- **Molecular formula:** C27H36N4O5S
- **Molecular weight:** 528.7 g/mol
- **CAS number:** 159634-47-6
- **Also known as:** Ibutamoren, MK-0677, L-163,191, Nutrobal, Ibutamoren mesylate
- **Half-life:** Short plasma half-life per dose; once-daily oral dosing nonetheless elevated mean 24-hour GH and sustained IGF-1 increases throughout the trial periods
- **Solubility:** Non-peptide small molecule with oral bioavailability; administered as an oral preparation in clinical trials
- **Storage:** Store the solid compound at room temperature protected from light and moisture.

## Mechanism of Action

MK-677 is a potent, orally active agonist of the growth hormone secretagogue receptor GHSR-1a, the receptor for the endogenous hormone ghrelin. Acting on pituitary somatotrophs and hypothalamic neurons, it amplifies the amplitude of endogenous pulsatile GH release rather than replacing it with continuous elevation: in elderly subjects, 25 mg/day increased mean 24-hour GH concentrations by 97 +/- 23% through higher pulse height and interpulse nadir levels without changing pulse number. Downstream, serum IGF-1 rises into the range of healthy young adults and remains elevated with continued daily dosing. As a ghrelin mimetic, MK-677 also stimulates appetite, and longer exposure produces modest increases in cortisol and fasting glucose, the main trade-offs of chronic GHSR activation.

## Key Research Findings

- MK-677 is not a peptide but an orally active small-molecule ghrelin receptor (GHSR-1a) agonist, grouped with GHRPs because it drives the same pulsatile GH release pathway.
- In adults aged 64-81, 25 mg daily increased mean 24-hour GH by 97 percent and restored IGF-1 to the young-adult range (141 to 265 µg/L at 4 weeks).
- A 2-year randomized trial found 1.1 kg fat-free mass gain versus placebo in older adults, but no improvement in strength or function, alongside increased appetite, mild edema, and reduced insulin sensitivity.
- MK-677 has no approved indication in any country and is named on the WADA Prohibited List under section S2, prohibited at all times.

## MK-677 Pharmacokinetics: The Oral Secretagogue

MK-677's development rationale was pharmacokinetic from the start: a non-peptide small molecule that survives oral dosing and stimulates the GH axis with once-daily administration, in contrast to the injectable growth hormone secretagogue peptides. The published human record characterizes exposure mainly through pharmacodynamic endpoints — GH pulse amplitude and IGF-1 — measured across trials lasting up to two years.

### Oral Bioavailability by Design

MK-677 emerged from a deliberate reverse-pharmacology program whose target product profile was an oral, once-daily drug.

- Design Objective: The growth hormone secretagogue program explicitly sought small molecules with pharmacokinetics suitable for once-daily oral administration that would rejuvenate the GH/IGF-I axis, working backward from function rather than from a known receptor (PMID 15814848).
- Discovery Data: L-163,191 (MK-0677) was selected for clinical development because it released GH from rat pituitary cells at an EC50 of 1.3 nM and elevated GH in dogs after oral doses as low as 0.125 mg/kg — oral activity being the property that distinguished it from the peptide secretagogues such as GHRP-6 that it mechanistically mimics (PMID 7624358).
- Analytical Capability: A liquid chromatography-tandem mass spectrometry assay was developed capable of quantifying MK-677 in human plasma at picogram levels, establishing that systemic exposure after oral dosing was measurable and trackable in clinical studies (PMID 9200526).

### GH and IGF-1 Exposure Kinetics

Because formal plasma pharmacokinetic parameters were not the focus of the published trials, the exposure profile is defined by hormonal response kinetics.

- Acute GH Response: A single 25 mg oral dose produced a peak GH response of 55.9 +/- 31.7 µg/L; after a week of daily dosing the peak was 22.6 +/- 9.3 µg/L versus approximately 7-9 µg/L on placebo — the acute peak attenuates with continued dosing while axis elevation persists (PMID 9467534).
- Dose-Dependent Axis Elevation: In adults aged 64-81, 2 weeks of once-daily MK-677 increased mean 24-hour GH dose-dependently, with 25 mg/day producing a 97 +/- 23% rise driven by higher pulse amplitude and interpulse nadir concentrations, with pulse number unchanged (PMID 8954023).
- Slow IGF-1 Build: Serum IGF-1 rose gradually on the same schedule, from 141 +/- 21 µg/L at baseline to 219 +/- 21 µg/L at 2 weeks and 265 +/- 29 µg/L at 4 weeks — hepatic IGF-1 output integrating several days of GH stimulation rather than tracking each dose (PMID 8954023).
- Sustained IGF-1 Under Caloric Stress: In calorically restricted volunteers, 7 days of 25 mg/day held mean IGF-1 at 264 +/- 31 ng/mL versus 188 +/- 19 ng/mL on placebo, with IGFBP-3 rising in parallel to 3,273 versus 2,604 ng/mL (PMID 9467534).

### Long-Run Exposure and the Missing Plasma Half-Life

The longest controlled exposure data for any GH secretagogue come from the 2-year elderly trial; the plasma half-life itself is not definitively published.

- Two-Year Durability: Once-daily 25 mg dosing maintained GH and IGF-1 in the young-adult range across 24 months of treatment without escape or tachyphylaxis, alongside a 1.1 kg fat-free mass increase versus a 0.5 kg decline on placebo (PMID 18981485).
- Once-Daily Justification: The once-daily schedule used across the clinical program rests on the pharmacodynamic observation that a single oral dose elevates GH pulse amplitude and sustains IGF-1 elevation across 24 hours and beyond, not on a formally reported plasma elimination half-life (PMID 8954023).
- Honest Data Gap: Despite the existence of a validated picogram-level plasma assay, no peer-reviewed paper reports a definitive human plasma half-life, clearance, or volume of distribution for MK-677; specific half-life figures circulating online are not traceable to the published clinical literature (PMID 9200526).
- Exposure-Linked Metabolic Effects: Fasting glucose rose from 5.4 to 6.8 mmol/L over 4 weeks at 25 mg/day in the short-term elderly study and by 0.3 mmol/L over 12 months in the 2-year trial — a dose- and duration-linked pharmacodynamic cost of chronic GHSR-1a activation (PMID 8954023; PMID 18981485).

## Dosing Information (Research Context)

Published clinical trials administered MK-677 orally once daily, most commonly at 25 mg (studied range 2-25 mg), for durations from 2 weeks to 2 years. It is an investigational compound with no approved indication, and no standardized dosing exists outside research protocols.

| Route | Dose | Frequency | Notes |
| --- | --- | --- | --- |
| Oral (clinical trials) | 2–25 mg (25 mg most studied) | Once daily | Durations of 2 weeks to 2 years in published RCTs; investigational only, no approved indication as of 2026 |

## Researched Effects

- **GH and IGF-1 Elevation** (evidence: extensive): In a randomized, double-blind, placebo-controlled trial in 32 healthy subjects aged 64-81, once-daily oral MK-677 (2, 10, or 25 mg) for up to 4 weeks increased mean 24-hour GH by 97 +/- 23% at the 25 mg dose by enhancing pre-existing pulsatile secretion. Serum IGF-1 rose from 141 +/- 21 µg/L at baseline to 265 +/- 29 µg/L at 4 weeks at the 25 mg dose, restoring levels to the normal young-adult range. Fasting glucose increased from 5.4 to 6.8 mmol/L, prolactin rose 23% but remained within the normal range, and circulating cortisol did not change over this short exposure.
- **Fat-Free Mass Preservation in Older Adults** (evidence: extensive): A 2-year, double-blind, randomized, placebo-controlled trial in 65 healthy adults aged 60-81 tested MK-677 25 mg once daily. Over 12 months, fat-free mass increased by 1.1 kg in the MK-677 group while decreasing 0.5 kg on placebo (P<0.001), and body weight rose 2.7 kg versus 0.8 kg (P=0.003), with no significant difference in abdominal visceral fat or total fat mass. The honest caveat: the increased fat-free mass did not produce measurable improvements in strength or physical function, so body-composition benefit should not be equated with proven functional benefit. Two-year exploratory analyses confirmed the 1-year findings.
- **Increased Bone Turnover** (evidence: moderate): In a randomized, double-blind, placebo-controlled trial in 24 healthy obese males aged 19-49, MK-677 25 mg/day for 8 weeks increased markers of bone formation (carboxy-terminal propeptide of type I procollagen +23%, procollagen III peptide +28%, osteocalcin +15% at 8 weeks) and markers of bone resorption (carboxy-terminal telopeptide of type I collagen +26%, urinary hydroxyproline/creatinine +23%), alongside a 43-44% rise in IGFBP-5. The pattern indicates activation of bone remodeling rather than demonstrated net gains in bone mass, which would require longer study to establish.
- **Sleep Architecture Effects** (evidence: moderate): In placebo-controlled crossover work, high-dose MK-677 (25 mg at bedtime) increased stage IV (deep) sleep duration by approximately 50% and REM sleep by more than 20% in healthy young adults, while deviations from normal sleep fell from 42% under placebo to 8%. In subjects aged 65-71, treatment increased REM sleep by nearly 50% and shortened REM latency. These findings link ghrelin receptor activation to sleep regulation and are consistent with the known coupling between sleep and somatotropic activity.
- **Appetite Stimulation and Glucose Effects** (evidence: moderate): Ghrelin is the body's principal hunger signal, and MK-677 reproduces this effect: increased appetite was the most frequent side effect in the 2-year elderly trial, subsiding over a few months. The metabolic trade-offs include a mean fasting glucose increase of 0.3 mmol/L and decreased insulin sensitivity over 12 months in older adults, consistent with the 5.4 to 6.8 mmol/L fasting glucose rise seen over 4 weeks in the earlier elderly study. Transient mild lower-extremity edema and muscle pain were the other common complaints. These effects frame the main safety considerations for chronic GH secretagogue use.

## Research Applications

- Growth Hormone Axis Research
- Sarcopenia and Aging Studies
- Ghrelin Receptor Pharmacology
- Bone Metabolism Research
- Sleep Physiology

## Key Studies

### Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial

Nass R, Pezzoli SS, Oliveri MC, et al. — *Annals of Internal Medicine* (2008) — [PMID 18981485](https://pubmed.ncbi.nlm.nih.gov/18981485/) | [doi:10.7326/0003-4819-149-9-200811040-00003](https://doi.org/10.7326/0003-4819-149-9-200811040-00003)

This 2-year, double-blind, randomized, placebo-controlled, modified-crossover trial gave 65 healthy adults aged 60-81 MK-677 25 mg or placebo once daily. MK-677 increased GH and IGF-1 levels into the young-adult range without serious adverse effects. Fat-free mass increased 1.1 kg versus a 0.5 kg decrease on placebo (P<0.001) and body weight rose 2.7 kg versus 0.8 kg (P=0.003), with no significant change in visceral or total fat mass. Fasting glucose rose 0.3 mmol/L and insulin sensitivity decreased; cortisol increased 47 nmol/L; the most frequent side effects were increased appetite, transient mild lower-extremity edema, and muscle pain. Increased fat-free mass did not translate into changes in strength or function.

### 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

Chapman IM, Bach MA, Van Cauter E, et al. — *Journal of Clinical Endocrinology and Metabolism* (1996) — [PMID 8954023](https://pubmed.ncbi.nlm.nih.gov/8954023/) | [doi:10.1210/jcem.81.12.8954023](https://doi.org/10.1210/jcem.81.12.8954023)

In this randomized, double-blind, placebo-controlled trial, 32 healthy subjects aged 64-81 received placebo or MK-677 2, 10, or 25 mg orally once daily in study periods of 14 and 28 days. The 25 mg dose increased mean 24-hour GH by 97 +/- 23% by enhancing pre-existing pulsatile secretion (higher pulse height and nadir, unchanged pulse number), and raised IGF-1 from 141 +/- 21 to 265 +/- 29 µg/L at 4 weeks, into the young-adult range. Fasting glucose rose from 5.4 to 6.8 mmol/L, prolactin increased 23% within the normal range, and cortisol was unchanged, establishing once-daily oral MK-677 as an effective GH axis stimulant in older people.

### Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males

Svensson J, Ohlsson C, Jansson JO, et al. — *Journal of Bone and Mineral Research* (1998) — [PMID 9661080](https://pubmed.ncbi.nlm.nih.gov/9661080/) | [doi:10.1359/jbmr.1998.13.7.1158](https://doi.org/10.1359/jbmr.1998.13.7.1158)

This randomized, double-blind, placebo-controlled trial treated 24 healthy obese males aged 19-49 (BMI over 30) with MK-677 25 mg/day or placebo for 8 weeks. MK-677 increased bone formation markers (type I procollagen carboxy-terminal propeptide +23%, procollagen III peptide +28% within 2 weeks, osteocalcin +15% at 8 weeks) and resorption markers (type I collagen carboxy-terminal telopeptide +26%, urinary hydroxyproline/creatinine +23%, calcium/creatinine +46%), with IGFBP-5 up 43-44%. The authors concluded short-term MK-677 activates bone turnover and called for long-term studies to determine whether bone mass increases.

### Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man

Copinschi G, Leproult R, Van Onderbergen A, et al. — *Neuroendocrinology* (1997) — [PMID 9349662](https://pubmed.ncbi.nlm.nih.gov/9349662/) | [doi:10.1159/000127249](https://doi.org/10.1159/000127249)

This placebo-controlled crossover study examined bedtime MK-677 administration in 8 young adults (18-30 years, 7-day periods, 5 and 25 mg) and 6 older subjects (65-71 years, 14-day periods, 2 then 25 mg). In young subjects, high-dose MK-677 increased stage IV sleep duration by approximately 50% and REM sleep by more than 20%, while deviations from normal sleep fell from 42% under placebo to 8%. In older adults, REM sleep increased nearly 50% with decreased REM latency and fewer deviations from normal sleep. The findings suggest MK-677 can simultaneously improve sleep quality and correct the relative hyposomatotropism of aging.

## Frequently Asked Questions

### Is MK-677 a peptide?

No. MK-677 (ibutamoren) is a non-peptide, small-molecule spiropiperidine (formula C27H36N4O5S) that is orally active. It appears alongside growth hormone secretagogue peptides such as ipamorelin, GHRP-6, and hexarelin only because it targets the same receptor, GHSR-1a, and produces the same downstream effect: increased pulsatile GH and IGF-1. Its small-molecule nature is precisely why it can be taken by mouth while peptide secretagogues must be injected.

### What did the 2-year MK-677 trial in older adults show?

The Nass trial (Annals of Internal Medicine 2008) randomized 65 healthy adults aged 60-81 to MK-677 25 mg or placebo once daily. Over 12 months, MK-677 raised GH and IGF-1 into the young-adult range and increased fat-free mass by 1.1 kg versus a 0.5 kg loss on placebo, without serious adverse effects. However, the extra fat-free mass did not improve strength or function, fasting glucose rose slightly, insulin sensitivity decreased, and appetite, transient edema, and muscle pain were common. The authors called for longer functional and pharmacoeconomic studies, which were never completed.

### How much does MK-677 raise GH and IGF-1?

In the Chapman study (JCEM 1996) in adults aged 64-81, 25 mg/day increased mean 24-hour GH concentrations by 97 +/- 23% after 2 weeks, driven by higher GH pulse amplitude and nadir levels with unchanged pulse frequency. Serum IGF-1 rose from a baseline of 141 +/- 21 µg/L to 265 +/- 29 µg/L at 4 weeks, squarely within the normal range for young adults. Lower doses (2 and 10 mg) produced smaller, dose-dependent increases.

### Does MK-677 raise cortisol or prolactin?

Modestly, with nuance by exposure length. Over 4 weeks in elderly subjects, Chapman and colleagues found no change in circulating cortisol and a 23% prolactin increase that stayed within the normal range. Over 12 months in the 2-year trial, cortisol increased by 47 nmol/L (P=0.020), a statistically real but small effect. This profile is milder than older secretagogues such as GHRP-2 and GHRP-6, which acutely elevate both cortisol and prolactin, but less selective than ipamorelin, which does not meaningfully affect either.

### Does MK-677 build muscle?

It increases measured fat-free mass, but that is not the same as proven functional muscle gain. In the 2-year elderly trial, fat-free mass increased 1.1 kg versus placebo, yet strength and physical function did not improve. Some of the fat-free mass increase likely reflects water and body cell mass rather than contractile tissue. No trial has demonstrated that MK-677 improves strength, performance, or frailty outcomes, which is central to why it never advanced to approval.

### Why was MK-677 never approved as a drug?

Merck developed MK-677 through Phase 2 trials in the 1990s and 2000s but did not bring it to market. The published record suggests the core problem: it reliably raises GH and IGF-1 and increases fat-free mass, but without demonstrated functional benefit in older adults, and with trade-offs of increased appetite, mild edema, reduced insulin sensitivity, and rising fasting glucose on chronic dosing. Without a clear clinical outcome advantage, the long-term benefit-risk profile did not support an approval program.

### How does MK-677 compare with injectable GHRPs like ipamorelin?

The practical differences are route and selectivity. MK-677 is orally active and taken once daily, while ipamorelin and other GHRPs are injectable peptides given one to three times daily. MK-677 stimulates appetite strongly (it is a ghrelin mimetic) and modestly raises cortisol with chronic use; ipamorelin is comparatively selective, producing GH release without meaningful appetite, cortisol, or prolactin effects. MK-677 also has by far the deepest human trial record of any secretagogue, including 2-year data, which no GHRP peptide can match.

### Is MK-677 legal or prohibited in sport?

MK-677 is not approved for human use by the FDA, EMA, TGA, or any other major regulator, so products sold online are unregulated research chemicals of uncertain purity and dose. In sport, ibutamoren is named on the WADA Prohibited List under section S2 (peptide hormones, growth factors, related substances and mimetics) and is prohibited at all times, in and out of competition.

## Related Peptides

- [Ipamorelin](https://peptpedia.org/peptide/ipamorelin)
- [CJC-1295](https://peptpedia.org/peptide/cjc-1295)
- [GHRP-6](https://peptpedia.org/peptide/ghrp-6)
- [Hexarelin](https://peptpedia.org/peptide/hexarelin)

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This content is for educational and research purposes only. It is not medical advice, and the compounds covered are research chemicals not approved for human use unless explicitly stated otherwise.

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