B
Tier
Oral non-peptide GH secretagogue that raises GH and IGF-1.
Small molecule, not a peptide
WADA Status:
Prohibited at all times (S2)
Human Trial Scoreboard
Completed human RCTs
Phase 2 only, no Phase 3
Largest Human Study
Hip-fracture Ph2b, n=123
Longest exposure
2 years
Most Recent Trial
Merck-era trials
Description
MK-677, or ibutamoren, is not a peptide at all. It is an orally active small molecule from a class called spiropiperidines, and it mimics ghrelin to prompt growth hormone release. Its history is the most instructive pharmaceutical story in this database. Merck developed it across roughly six separate indications including growth hormone deficiency, osteoporosis, muscle loss, obesity, hip fracture recovery and Alzheimer's disease. It did exactly what it was designed to do, raising IGF-1 reliably, and it repeatedly failed to make patients functionally better. In a trial of one hundred and twenty three elderly hip fracture patients, congestive heart failure occurred in four of sixty two treated patients against one of sixty one on placebo, and the trial was stopped early. Merck never filed for approval. It also worsens insulin sensitivity.
What Are The Claims
Claims made for this compound: Raises GH and IGF-1 with once-daily oral dosing (human RCTs); Increases fat-free mass (two-year trial); Deepens sleep in some; Increases appetite
Evidence
This compound has more human data than almost anything else here, and the data is the argument against it. Nass and colleagues, publishing in the Annals of Internal Medicine in 2008, ran a two-year randomized trial in healthy older adults. Fat-free mass rose by 1.1 kg, which is the result the marketing cites. The same trial found that insulin sensitivity declined and mean serum glucose rose by 0.28 mmol per litre, roughly 5 mg/dL. An earlier study by Chapman and colleagues in 1996 found fasting glucose rising from 5.4 to 6.8 mmol per litre over four weeks in elderly participants. Peripheral edema was common in older participants, and a hip-fracture trial population raised a congestive heart failure signal. The honest summary is that MK-677 does what it says regarding growth hormone and lean mass, and carries a diabetogenic effect that came out of the same trials. Both halves belong in the description.
Evidence Strength
Moderate (human RCTs)
Caveats
Small molecule, NOT a peptide; not approved; Merck halted development; a congestive-heart-failure signal appeared in the hip-fracture trial; worsens insulin sensitivity.
Safety
Alternative Measures
Legal Status
US
Not approved; excluded from supplements by statute
UK
Not approved
EU
Not approved
AU
Not approved
WADA
Prohibited at all times (S2)
Not approved. Merck discontinued development. WADA-prohibited. Sold widely as a research chemical.
Citations
Nass R et al. (2008). Annals of Internal Medicine. Two-year randomized trial in healthy older adults; declined insulin sensitivity, serum glucose increase of 0.28 mmol/L. PMID: 18981485. | Chapman IM et al. (1996). Fasting glucose increase 5.4 to 6.8 mmol/L over four weeks in elderly subjects. PMID: 8954023.