MK-677 (Ibutamoren) : données probantes, mécanisme et limites

MK-677, also called ibutamoren or MK-0677, is not a peptide. It is an orally active small molecule that activates the ghrelin receptor, GHS-R1a. It is often grouped with growth hormone peptides because it acts on the same hormone axis.

Being active by mouth does not make it a supplement. FDA lists ibutamoren as excluded from the dietary supplement definition and has sent warning letters to companies selling it.

A structural study resolved how ibutamoren binds the human ghrelin receptor and stabilizes its active signaling state. In the hypothalamus and pituitary, activation of this receptor promotes pulsed release of the body's own growth hormone and raises IGF-1. This is laboratory and human biomarker evidence.

The same receptor takes part in appetite, energy balance, and glucose regulation, so the effects are broader than a selective growth hormone signal. That helps explain why a rise in IGF-1 can coexist with limited functional benefit or with important adverse events.

A multicenter randomized trial in people with mild to moderate Alzheimer disease found that IGF-1 rose, yet there was no significant difference from placebo on any of its clinical measures over 12 months. The authors concluded it was ineffective at slowing disease progression.

A randomized phase IIb trial in older adults recovering from hip fracture found higher IGF-1 and better gait speed, but no improvement in most other functional measures. Fewer falls in the treated group did not reach statistical significance. The trial was terminated early because of a safety signal of congestive heart failure in a limited number of patients. The authors judged its safety profile unfavorable in that population.

A 2018 narrative review of growth hormone secretagogues found few long-term, rigorously controlled studies. It summarizes the class rather than proving a benefit for ibutamoren. No trial has established improved strength, healing, cognition, or longevity.

Clinical studies have reported appetite changes, fluid retention, and impaired glucose handling in susceptible groups. The 2018 review notes concern about rising blood glucose from reduced insulin sensitivity, and calls for long-term safety data, including cancer incidence and mortality.

The hip-fracture trial stopped over a congestive heart failure signal, which FDA cites in its compounding safety-risk list. A 2025 case report describes raised liver enzymes (transaminitis) in an otherwise healthy man in his early 30s, which returned to normal after he stopped. A single case is a safety signal; it cannot estimate how often this happens.

Ibutamoren is not approved by FDA or Health Canada. FDA places ibutamoren mesylate in category 2 for compounding under both the 503A and 503B interim policies. WADA prohibits it in and out of competition as a growth hormone secretagogue.