MK-677
Also known as: Ibutamoren, Ibutamoren mesylate, MK-0677, L-163191
An orally-active, non-peptide GH secretagogue that durably raises growth hormone and IGF-1 in humans — the best-studied compound in this class. Reached late-stage Merck trials but was never approved because it failed to deliver clinical benefit. Sold today as a gray-market research chemical.
Never FDA-approved for any indication. Developed by Merck through Phase III trials (for conditions including frailty and Alzheimer's disease) that did not meet efficacy endpoints; development was discontinued. Now widely sold as a research chemical / gray-market supplement despite never being approved.
What it is
MK-677, also called ibutamoren, is an orally-active, non-peptide growth hormone secretagogue. Unlike the injectable GHRPs, it survives oral dosing and works as a once-daily tablet, activating the ghrelin receptor (GHS-R1a) to raise growth hormone (GH) and IGF-1 in a sustained way. It was developed by Merck in the 1990s as an oral alternative to injected GH and, unusually for a compound now sold as a “research chemical,” it has real late-stage human trial data.
What it’s approved or studied for
MK-677 is not approved anywhere for any indication. Merck took it through Phase III trials for conditions including frailty in older adults and Alzheimer’s disease. It engaged its target — IGF-1 rose as expected — but it failed to produce the clinical benefits those trials were designed to show, and development was discontinued. It is now sold gray-market as a supplement or research chemical despite never clearing approval.
What human evidence exists
This is the crucial distinction for MK-677: the biomarker effect is well established, but the clinical payoff is not. Multiple randomized trials, including a 2-year study in healthy older adults, show it durably raises GH and IGF-1 to youthful levels (Grade B). It increases fat-free mass — but much of that is body water, and it did not improve strength or physical function (Grade C for lean mass, Grade E for function). Its Alzheimer’s trial showed no clinical benefit despite clear target engagement (Grade E). No human data support anti-aging or longevity claims (Grade E). Long-term safety for unsupervised use is Grade U — unknown.
The major unknowns
The core unknown is whether restoring youthful GH/IGF-1 levels does anything worthwhile — the trials that tested this said no for the outcomes that mattered. Long-term effects of chronically elevated IGF-1 are uncertain and a theoretical concern. And because most MK-677 is sold outside any regulated supply chain, product identity, dose accuracy, and purity are not guaranteed.
Most important safety considerations
MK-677 consistently increases appetite and causes fluid retention, and trials found it worsened insulin sensitivity and fasting glucose — a meaningful concern for anyone with, or at risk of, diabetes. Fluid retention is a particular hazard in people with heart problems; a frail-elderly program was affected by adverse-event signals including congestive heart failure. It is prohibited in sport under WADA’s S2 category (ibutamoren is named explicitly), it is not approved for human use, and gray-market product quality is uncontrolled. This page summarizes the research record; it is not medical advice or an endorsement of use.
Evidence by outcome
Each outcome is graded on its own evidence — a compound can be strong for one use and unproven for another. See how we grade.
Durably raises GH and IGF-1 in humans across multiple controlled trials — the strongest evidence in this class. — In randomized studies, including a 2-year trial in healthy older adults, daily oral MK-677 raised GH and IGF-1 to levels seen in young adults, with a normal pulsatile pattern. This is a well-replicated biomarker effect.
Increases fat-free mass in trials, but much of the gain is body water, not proven functional muscle. — The 2-year older-adult trial showed increased fat-free mass and body weight — but no improvement in muscle strength or physical function, and a share of the "lean" gain reflects fluid retention.
Not demonstrated — trials specifically failed to show functional benefit. — Despite raising GH, IGF-1, and fat-free mass, controlled trials found no effect on thigh muscle area, strength, or function.
A Phase III trial showed no clinical benefit. — Despite clear IGF-1 elevation (target engagement), MK-677 did not slow the rate of progression of Alzheimer disease in a randomized trial.
No human evidence; raising IGF-1 is not established to extend healthspan.
Unknown — no long-term safety data support unsupervised use. — Trials noted increased appetite, fluid retention, and worsened insulin sensitivity / fasting glucose. In a frail-elderly hip-fracture program, an imbalance in adverse events (including congestive heart failure signals) contributed to halting development.
Safety
Common adverse effects
- Increased appetite
- Fluid retention / edema
- Fatigue or lethargy
- Increased fasting glucose and reduced insulin sensitivity
- Muscle or joint discomfort
Serious risks
- Worsened glucose tolerance / risk of impaired insulin sensitivity
- Fluid retention with potential to unmask or worsen heart failure in vulnerable people
- Sustained IGF-1 elevation of uncertain long-term consequence
- Unregulated product quality and contamination risk
Contraindications
- Not approved for human therapeutic use; caution flags in trial populations included heart failure risk and impaired glucose tolerance — no formal contraindication labeling exists
References
- Nass R et al. Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized Trial (MK-677). Annals of Internal Medicine (2008)
- Murphy MG et al. 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)
- Sevigny JJ et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology (2008)
- WADA. The Prohibited List (S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics)