MK-677

Dosing from the Literature

Published for muscle and growth hormone: 25 mg a day by mouth, the dose in Merck's trials, including a 12-month one (Murphy et al., 2001). Not published: an approved dose; it was never approved.

Trial doses below are cited with the people they were given to; the other figures are what clinic and online guides describe. MK-677 is not FDA-approved and there is no labeled human dose.

What It Is

MK-677, also known as ibutamoren (and historically as L-163,191), is an orally active, non-peptide small molecule that mimics the action of the hormone ghrelin at the growth hormone secretagogue receptor (GHSR-1a). It was discovered and developed by Merck Research Laboratories in the 1990s as part of a program to find an oral growth hormone secretagogue — a drug that could elevate endogenous growth hormone (GH) and downstream IGF-1 through a natural pulsatile mechanism, without the injection burden and peaks of recombinant GH therapy.

Mechanistically, MK-677 is often grouped with peptide ghrelin-receptor agonists like GHRP-6, GHRP-2, hexarelin, and ipamorelin. Functionally, it is distinct from all of them in one decisive way: MK-677 is orally bioavailable, while the peptide secretagogues all require subcutaneous injection. That single feature has made MK-677 the most widely used growth-hormone-axis compound in community and "biohacking" settings despite being chemically a small molecule rather than a peptide.

Merck advanced MK-677 through multiple Phase 2 and Phase 3 trials across several indications — GH deficiency in adults, frailty and functional impairment in older adults, post-hip-fracture recovery, obesity, and postmenopausal osteoporosis — before discontinuing the program without a commercial approval. The published human dataset includes the widely-cited 12-month randomized controlled trial of 65 healthy older adults by Nass et al. (Ann Intern Med 2008; PMID 18981485), the Murphy postmenopausal osteoporosis trials, the Bach and Adunsky hip-fracture studies, and the Svensson obesity study. This is one of the most comprehensive human datasets of any GH-axis agent still used off-label, which is part of why it remains so influential in the "research" space.

MK-677 is not FDA-approved, is banned by the World Anti-Doping Agency (WADA), and was added to the FDA 503A Category 2 Bulk Drug Substances list on September 29, 2023, making it ineligible for use by traditional compounding pharmacies under sections 503A/503B. Despite this, products containing it are sold labeled as dietary supplements, as research chemicals or "For Research Use Only" (Operation Supplement Safety).

Mechanism of Action

MK-677 is pharmacologically a ghrelin mimetic: it activates the receptor that ghrelin acts on, which drives GH release and appetite (Nass et al., 2008). The downstream endocrine phenotype is specific and well-characterized.

• GHSR-1a agonism (primary mechanism) — MK-677 activates the growth hormone secretagogue receptor type 1a, the ghrelin receptor. In rat pituitary cells it released GH at nanomolar concentrations (EC50 1.3 nM), by the same mechanism as the peptide GHRP-6 (Patchett et al., 1995). The receptor is coupled to Gq- and Gi-family G proteins and activates phospholipase C (Sigalos & Pastuszak, 2018). A 2021 cryo-EM structural paper (Nature Communications) resolved ibutamoren and ghrelin each bound to the receptor: ibutamoren sits mainly in the bottom of the pocket ghrelin uses, with its own hydrogen-bond contacts.
• GH pulse amplitude + frequency — In older adults, MK-677 raised the height of the body's own GH pulses without changing their number (Chapman et al., 1996; Thorner et al., 1997); in 9 young men it raised pulse frequency, mostly by adding small pulses (Copinschi et al., 1996). Over 12 months it raised GH and IGF-1 in older adults to young-adult levels, with GH release still pulsatile (Nass et al., 2008).
• GHRH (the signal that tells the pituitary to release GH) synergy — GHRH and GH-releasing peptides given together release more GH than either alone, and a review describes GHRH analogs such as sermorelin and tesamorelin as acting synergistically with ibutamoren (Sigalos & Pastuszak, 2018).
• IGF-1 elevation (downstream) — GH drives IGF-1 production, mainly through GH receptors in the liver (Sigalos & Pastuszak, 2018). In older adults on 25 mg, IGF-1 rose 55% by 2 weeks and 88% by 4 weeks, into the young-adult range (Chapman et al., 1996); at 12 months it was 1.5 times baseline, within the young-adult range in 22 of 43 (Nass et al., 2008).
• Appetite stimulation — Ghrelin acts on appetite as well as on GH, and in the 12-month trial 67% of people on MK-677 reported more appetite vs 36% on placebo (Nass et al., 2008).
• Cortisol and prolactin — In dogs it raised GH without significant effects on prolactin, aldosterone, LH or thyroxine, and cortisol rose only modestly (Patchett et al., 1995). In older adults, cortisol did not change and prolactin rose 23%, within the normal range (Chapman et al., 1996); over 12 months, mean 24-hour cortisol rose 47 nmol/L (Nass et al., 2008).
• Sleep — In a crossover study on 25 mg a day, stage 4 (deep) sleep rose about 50% and REM sleep more than 20% in 8 young men, and REM sleep rose about 50% in 6 older men (Sigalos & Pastuszak, 2018). Online guides describe vivid dreams.
• Insulin signaling modulation — GH antagonizes insulin action (Sigalos & Pastuszak, 2018). In the 12-month trial, fasting glucose and HbA1c rose and insulin sensitivity fell (Nass et al., 2008).

What the Research Shows

The MK-677 human evidence base is unusually deep for a non-approved compound because Merck ran a serious clinical development program. Key findings:

• Healthy older adults — 12-month RCT (Nass et al., Ann Intern Med 2008; PMID 18981485) — 65 healthy adults aged 60–81 randomized to MK-677 25 mg/day vs placebo for 12 months. Results: GH and IGF-1 restored to healthy-young-adult levels, fat-free mass increased by 1.1 kg (vs −0.5 kg placebo), no improvement in strength or physical function, and worsening of insulin sensitivity.
• Postmenopausal osteoporosis (Murphy et al., JCEM 2001; PMID 11238495) — 292 women with osteoporosis randomized to alendronate, MK-677, combination, or placebo for 12–18 months. MK-677 alone did not produce significant BMD gains at most sites; combination with alendronate attenuated alendronate's suppressive effect on bone formation but did not add BMD at sites other than femoral neck.
• Elderly bone turnover (Murphy et al., JBMR 1999) — 187 healthy and functionally impaired elderly adults. MK-677 increased osteocalcin and urinary N-telopeptide (markers of bone turnover), consistent with amplified bone remodeling without clear net BMD effect.
• Obese young males (Svensson et al., JCEM 1998; PMID 9661080) — 8-week trial with MK-677 in obese subjects. Increases in GH, IGF-1, fat-free mass, and energy expenditure; increases in bone turnover markers.
• Hip fracture recovery — Bach trial — Randomized, double-blinded, placebo-controlled study of MK-677 in elderly hip-fracture recovery. Measured functional outcomes and safety over 6 months.
• Hip fracture recovery — Adunsky trial — Parallel study in 123 elderly hip-fracture patients, terminated early due to an observed increase in congestive heart failure (6.5% ibutamoren vs 1.7% placebo). Of the longer trials of MK-677, it is the only one that found significant adverse effects (Sigalos & Pastuszak, 2018).
• GH deficiency adults — Merck-era Phase 2 trials showed MK-677 restored GH/IGF-1 in adult GHD patients with oral dosing, supporting the original development hypothesis.
• Short-term studies — In studies of 1 to 9 weeks at doses up to 50 mg a day, IGF-1 rose in healthy young men (Copinschi et al., 1996) and in older adults (Chapman et al., 1996; Murphy et al., 1999).
• Structural pharmacology (Nature Communications 2021) — Cryo-EM characterization of ibutamoren bound to GHSR-1a, clarifying the shared binding pocket with ghrelin and informing structure-based design of next-generation agonists.

Human Data

MK-677 is one of the more heavily human-studied compounds in the GH-axis space. Published trials span healthy older adults, frail adults, hip-fracture recovery, postmenopausal osteoporosis, obesity, and adult GHD.

• Nass 2008 — 12-month healthy older adults, 25 mg; definitive FFM + IGF-1 effect; insulin sensitivity worsening.
• Murphy 1999 / 2001 — Multi-cohort bone studies; modest bone-formation signal; limited net BMD benefit.
• Svensson 1998 — Obese young adult trial; clear anabolic + metabolic signal over 8 weeks.
• Bach hip fracture — 6-month functional recovery trial.
• Adunsky hip fracture — Terminated early due to CHF imbalance.
• Merck Phase 2 GHD — Short-duration endocrine response studies.
• Alzheimer's disease — A 12-month trial in 563 patients with mild to moderate Alzheimer's disease; adverse events that stopped treatment were similar on MK-677 and placebo (11.3% vs 10.4%) (Sigalos & Pastuszak, 2018).
• PharmacoVigilance (post-abandonment) — Community and practitioner case series describing water retention, fatigue, elevated fasting glucose, and appetite increase consistent with published trials.

Most of the published human data are Merck-era, from roughly 1996 through the mid-2000s. Newer trials are registered on ClinicalTrials.gov: Phase 2 trials of LUM-201 (ibutamoren mesylate) in children with growth hormone deficiency (NCT04614337) and in nonalcoholic fatty liver disease (NCT05364684) have finished and posted results, and a Phase 3 trial in children with growth hormone deficiency has been recruiting since May 2026 (NCT06948214).

Reconstitution & Storage

Unlike peptide secretagogues, MK-677 is an oral small molecule. There is no reconstitution step. The trials used 25 mg tablets, with 10 mg tablets for dose reductions (Nass et al., 2008). Sellers list liquids at 25 mg/mL and capsules of 10 mg or 25 mg.

• Storage — Listings disagree on liquids: room temperature away from direct sunlight (a seller) or refrigerated (two online guides). Capsules: room temperature, dry (online guides).
• Shelf life — Listings disagree: 2–3 years for one seller's liquid, 6–12 months refrigerated for liquid in an online guide, and 24 months or more for sealed capsules.
• Timing — The trials gave it once a day, in the morning (Nass et al., 2008) or at bedtime (Copinschi et al., 1996); clinic and online guides describe bedtime dosing.

→ Calculator — vial-to-syringe math

Side Effects & Risks

Safety data come from trials lasting up to 2 years, most of them short and small (Sigalos & Pastuszak, 2018).

• Appetite stimulation — In the 12-month trial, 67% of people on MK-677 reported more appetite vs 36% on placebo; in half of them it returned to normal within 3 months (Nass et al., 2008).
• Water retention and edema — In the 12-month trial, mild, transient edema was recorded in 44% on MK-677 vs 27% on placebo, and total body water rose 1.7 kg vs 0.1 kg (Nass et al., 2008).
• Insulin sensitivity decline — In Nass 2008, 12 months of 25 mg MK-677 produced measurable insulin sensitivity decline and modest fasting-glucose increase. A 2018 review concludes that the trials support a higher risk of high blood sugar with GH secretagogues, with few other adverse effects directly attributable to them (Sigalos & Pastuszak, 2018).
• Fasting glucose / HbA1c increase — At 12 months on 25 mg, mean HbA1c rose 0.2 percentage points (vs a 0.1 fall on placebo) and fasting glucose 0.3 mmol/L (5 mg/dL) (Nass et al., 2008). In older adults, fasting glucose rose from 5.4 to 6.8 mmol/L within 4 weeks (Chapman et al., 1996).
• Congestive heart failure signal — The Adunsky trial, in 123 older hip-fracture patients given 25 mg a day or placebo, was stopped early when 4 on the drug (6.5%) and 1 on placebo (1.7%) developed heart failure; the drug group started with higher blood pressure, which may account for part of the difference (Adunsky et al., 2011; Sigalos & Pastuszak, 2018).
• Lethargy and fatigue — Online guides describe occasional lethargy in the first week, and grogginess after bedtime doses.
• Vivid dreams / sleep changes — Online guides describe vivid dreams, mostly in the first weeks. In a sleep study on 25 mg a day, deep and REM sleep increased (Sigalos & Pastuszak, 2018).
• Muscle and joint pain — In the 12-month trial, transient muscle pain was recorded in 33% on MK-677 vs 9% on placebo; joint pain was reported in both groups (58% vs 77%), and two women had their dose lowered for joint pain (Nass et al., 2008).
• Cancer concern (theoretical, IGF-1) — Studies have linked injected GH and higher IGF-1 levels with a higher risk of cancer, and as of 2018 no study had examined cancer rates with GH secretagogues (Sigalos & Pastuszak, 2018). In the 2-year trial, cancers were diagnosed in two people who had taken MK-677 and in one on placebo (Nass et al., 2008).
• WADA banned substance — Ibutamoren is explicitly listed as a banned Growth Hormone Secretagogue under S2 on the WADA Prohibited List.
• FDA Category 2 — Added to the FDA's Category 2 Bulk Drug Substances list, making it ineligible for legitimate compounding pharmacy use under 503A/503B.
• Unregulated products — It is an unapproved drug and not legal in dietary supplements, yet products are sold labeled as dietary supplements, as research chemicals or "For Research Use Only" (Operation Supplement Safety).

What to Expect — Timeline

What the trials measured, by time point:

• Weeks 2–4 — In a trial of 32 healthy adults aged 64–81, IGF-1 in those on 25 mg rose from 141 to 219 µg/L by week 2 and to 265 µg/L by week 4, and fasting glucose from 5.4 to 6.8 mmol/L (Chapman et al., 1996).
• First 3 months — In the 12-month trial, 67% of people on MK-677 reported more appetite vs 36% on placebo, and in half of them it returned to normal within 3 months; edema and muscle pain were mild and transient (Nass et al., 2008).
• 12 months — Fat-free mass rose 1.1 kg (vs a 0.5 kg fall on placebo) and body weight 2.7 kg (vs 0.8 kg); strength and function did not change (Nass et al., 2008).
• After stopping — IGF-1 was back at pretreatment levels one month after people switched to placebo, and the first year's changes reversed (Nass et al., 2008).

Quick Compare — MK-677 vs Ipamorelin vs CJC-1295 vs Sermorelin

MK-677 is in a cluster of four compounds that all elevate GH/IGF-1 by different mechanisms. Understanding which one fits which use case is the main practical question for anyone choosing among them.

Practical interpretation:

• Oral vs injection — MK-677 is the only oral option here. Convenience is its single biggest advantage. The other three are injected.
• Appetite — MK-677 drives appetite hard. Ipamorelin does not.
• Water retention and side-effect burden — MK-677 has the biggest water-retention and insulin-sensitivity footprint in this group. Ipamorelin is the cleanest.
• Pulsatility — GHRH+GHRP combinations (sermorelin + ipamorelin; CJC-1295 w/o DAC + ipamorelin) preserve natural pulse architecture better than chronic MK-677 exposure.
• Total IGF-1 response — MK-677 tends to produce the largest absolute IGF-1 rise. CJC-1295 with DAC produces sustained elevation. Sermorelin and ipamorelin are gentler.
• Safety profile — Among these four, ipamorelin and sermorelin have the cleanest safety data. MK-677 has the most robust efficacy data and the clearest side-effect data.

→ See full ipamorelin profile  •  → See full CJC-1295 profile  •  → See full sermorelin profile

Bloodwork & Monitoring

No label or clinical guideline sets monitoring for MK-677. In the 12-month trial, the investigators checked a complete blood count, a chemistry panel, HbA1c, fasting glucose, and PSA and testosterone in men, with yearly Pap smears and mammograms in women (Nass et al., 2008). A 2018 review recommends following IGF-1, body composition, blood glucose and HbA1c during GH-secretagogue treatment (Sigalos & Pastuszak, 2018).

Commonly Stacked With

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→ Calculator — vial-to-syringe math

Legal Status

Related Compounds

The GH-axis peptide cousins MK-677 competes with — plus the FDA-approved injected GH it was designed to replace.

Next Steps

References

1. Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE Jr, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO. 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. PMID: 18981485. DOI: 10.7326/0003-4819-149-9-200811040-00003.
2. Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ. 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. PMID: 11238495. DOI: 10.1210/jcem.86.3.7294.
3. Murphy MG, Bach MA, Plotkin D, Bolognese J, Ng J, Krupa D, Cerchio K, Gertz BJ. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. J Bone Miner Res. 1999;14(7):1182-1188. PMID: 10404019.
4. Svensson J, Lönn L, Jansson JO, Murphy G, Wyss D, Krupa D, Cerchio K, Polvino W, Gertz B, Boseaus I, Sjöström L, Bengtsson BA. 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. PMID: 9661080.
5. Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO. 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. PMID: 8954023.
6. Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, Szyper M, Caufriez A, Bosson D, L'Hermite M, Robyn C, Turek FW, Van Cauter E. Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men. J Clin Endocrinol Metab. 1996;81(8):2776-2782. PMID: 8768828.
7. Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA. 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. PMID: 21067829.
8. Bach MA, Rockwood K, Zetterberg C, Thamsborg G, Hébert R, Devogelaer JP, Christiansen JS, Rizzoli R, Ochsner JL, Beisaw N, et al.; MK 0677 Hip Fracture Study Group. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. 2004;52(4):516-523. PMID: 15066065.
9. Smith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, Wyvratt MJ Jr, Fisher MH, Nargund RP, Patchett AA. Peptidomimetic regulation of growth hormone secretion. Endocr Rev. 1997;18(5):621-645. PMID: 9331545.
10. Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G, 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. PMID: 7624358.
11. Shiimura Y, Horita S, Hamamoto A, Asada H, Hirata K, Tanaka M, Mori K, Uemura T, Kobayashi T, Iwata S, Kojima M. Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode. Nat Commun. 2020;11(1):4160. PMID: 32814772.
12. Shiimura Y, Horita S, Hamamoto A, Asada H, Hirata K, Tanaka M, Mori K, Uemura T, Kobayashi T, Iwata S, Kojima M. Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren. Nat Commun. 2021;12(1):6675.
13. Khojasteh-Bakht SC, Jones HM, Hirota T, Chen J, Lin DC, Harms AC, Vicini P, Cutler DL, Lalovic B. Pharmacokinetics of ibutamoren mesylate (MK-677) in healthy subjects. Br J Clin Pharmacol. 2005;59(5):595-602.
14. Thorner MO, Chapman IM, Gaylinn BD, Pezzoli SS, Hartman ML. Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging. Recent Prog Horm Res. 1997;52:215-246. PMID: 9238854.
15. Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018;6(1):45-53. PMID: 28400207.
16. Thomas JT, Sasaki R, et al. Growth Hormone Secretagogues as Potential Therapeutic Agents to Restore Growth Hormone Secretion in Older Subjects to Those Observed in Young Adults. J Gerontol A Biol Sci Med Sci. 2023;78(Suppl_1):38-46.
17. Lomenick B, et al. Ibutamoren: Structure, Function, and Clinical Implications. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
18. Operation Supplement Safety. Performance Enhancing Substance: MK-677 (Ibutamoren). U.S. Department of Defense Dietary Supplement Resource. opss.org.
19. WADA. 2026 Prohibited List. Section S2 — Peptide hormones, growth factors, related substances and mimetics. World Anti-Doping Agency.
20. FDA. Bulk Drug Substances That Raise Significant Safety Risks (Category 2). Pharmacy Compounding Advisory Committee. Updated 2025.
21. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
22. Stone W. The wellness world is eager for RFK Jr.’s promised move on peptides. NPR, March 31, 2026. npr.org/2026/03/31/nx-s1-5768206/peptides-rfk-fda-compounding-pharmacies. Read October 3, 2026. (The HHS secretary’s late-February podcast remarks, “about 14” peptides; reported, not a rule.)
23. Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, Fearon KC. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 2016;17(4):519-531. PMID: 26906526. DOI: 10.1016/S1470-2045(15)00558-6.

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