MK-677 (Ibutamoren)

Imagine a thermostat hack that genuinely cranks up the heating. The radiators get hot and the gauge climbs exactly as promised. But the house somehow never feels any warmer, the bills go up, and the boiler starts making worrying noises. MK-677 reliably moves the dials (GH and IGF-1) yet repeatedly failed to make anyone actually better off. Its maker switched it off.

Non-peptide agonist of the growth hormone secretagogue receptor (GHSR-1a), the ghrelin receptor. By mimicking ghrelin at the hypothalamus and pituitary it increases pulsatile GH secretion through enhanced GHRH signalling and suppressed somatostatin tone, driving downstream rise in hepatic IGF-1. It is orally bioavailable with prolonged half-life, distinguishing it from injectable peptide secretagogues.

Research contexts. Not proven uses, and not recommendations.

Several completed human RCTs exist. The landmark 2-year trial in healthy older adults (Nass et al. 2008) confirmed it raises GH/IGF-1 and adds roughly 1.6 kg of fat-free mass, but found no gain in strength, physical function or quality of life and worsened insulin sensitivity. A 563-patient Alzheimer's RCT (Sevigny et al. 2008) showed clear biomarker engagement (about 73% IGF-1 rise) yet zero clinical benefit on any cognitive or functional endpoint. A Phase 2b hip-fracture trial (Adunsky et al. 2011) showed marginal or inconsistent functional effects and was terminated early after a congestive-heart-failure safety signal. Merck ran these programmes and then discontinued development.

• !Not an approved medicine anywhere. Merck abandoned development after its trials failed to show clinical benefit.
• !Worsens insulin sensitivity and raises fasting glucose/HbA1c. A real diabetes-risk concern with sustained use.
• !Fluid retention and oedema. A congestive-heart-failure signal appeared in the hip-fracture trial and prompted early termination.
• !Sustained, non-physiological GH/IGF-1 elevation carries theoretical long-term risks (e.g. promoting growth of existing tumours). Long-term safety in healthy users is unknown.
• !Marked appetite stimulation and reports of lethargy or sleepiness are common.
• !Sold as an unlicensed research chemical with 'not for human consumption' labels to sidestep medicines law. No pharmaceutical-grade quality control over identity, purity or content.
• !WADA-prohibited at all times. Banned in sport.
• !Routinely marketed as a SARM or a peptide. It is neither.

Not a licensed medicine in the UK. It has no MHRA marketing authorisation and is not approved as a medicine anywhere in the world. It is an abandoned investigational drug now sold online as an unlicensed research chemical, typically labelled 'not for human consumption' to sidestep medicines law. Selling or supplying it for human use would fall foul of the Human Medicines Regulations 2012, which prohibit placing an unlicensed medicinal product on the market. It is not a controlled drug under the Misuse of Drugs Act, but it is neither legitimately obtainable nor prescribable. It is on the WADA Prohibited List as a growth hormone secretagogue.

• NCT00474279· Phase 2· Completed (published Nass et al. 2008)

  Effects of an Oral GH Secretagogue (MK-677) on Body Composition and Functional Ability of Older Adults

  The 2-year aging RCT in adults aged 60-81: positive on lean mass, null on function, negative on insulin sensitivity.

• · Phase 2· Completed, negative (Sevigny et al., Neurology 2008)

  MK-677 in mild-to-moderate Alzheimer's disease

  563 patients; target engagement (IGF-1 rise) without any clinical benefit.

• · Phase 2b· Completed, terminated early (Adunsky et al. 2011)

  MK-0677 for recovery after hip fracture

  Marginal functional effect; a CHF safety signal prompted early termination and contributed to programme discontinuation.

1. 01
   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)

   Landmark 2-year RCT (NCT00474279): raised GH/IGF-1 toward young-adult levels and added ~1.6 kg fat-free mass, but no improvement in strength/function and worsened insulin sensitivity.

2. 02
   Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial — Sevigny JJ, Ryan JM, van Dyck CH, et al., Neurology (2008)

   563-patient RCT in mild-to-moderate Alzheimer's; clear IGF-1 engagement (~73%) but no clinical benefit on any endpoint.

3. 03
   MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study — Adunsky A, Chandler J, Heyden N, et al., Archives of Gerontology and Geriatrics (2011)

   Phase 2b hip-fracture trial; marginal/inconsistent functional gains, and terminated early after a congestive-heart-failure safety signal.

4. 04
   Ibutamoren (MK-677) — overview, pharmacology and clinical development, PubMed search (background)