MK-677 (Ibutamoren)
Ibutamoren mesylate (MK-0677, L-163,191)
MK-677 (ibutamoren) is an orally active, non-peptide growth hormone secretagogue that mimics ghrelin at the GHS-R1a receptor, producing sustained increases in growth hormone and IGF-1 levels with once-daily dosing. Clinical trials show consistent lean mass gains but no robust functional improvements, and the compound carries risks including insulin resistance and, in frail elderly, congestive heart failure. Not FDA-approved for any indication.
Last updated: 2026-03-12
Safety Summary
Most common side effects (appetite increase, water retention) are most prominent in the first 1-2 weeks and may partially attenuate. Insulin resistance is dose-dependent and more concerning with chronic use, particularly in individuals with pre-existing metabolic risk. Community strategies: co-administration of berberine or metformin, dietary carbohydrate restriction, lower dosing (10 mg vs 25 mg). The CHF signal occurred in elderly, frail patients with potential pre-existing cardiovascular vulnerability. Long-term safety data beyond 1-2 years is limited. Sustained IGF-1 elevation raises theoretical concerns about tumor promotion, though no clinical data confirm this risk with MK-677 specifically. Monitoring of blood glucose and insulin sensitivity recommended
Known Side Effects
Very common (>50% in clinical trials and community)
Common (transient mild lower extremity edema)
Common (fasting glucose increase ~5 mg/dL average)
Common
Common (GH-related, similar to carpal tunnel symptoms)
Uncommon (especially first 1-2 weeks)
Common with chronic use
Rare but serious (led to hip fracture trial termination in elderly)
Rare (case reports)
Who Should NOT Use This
Phase IIb hip fracture trial (PMID 21067829) terminated early due to CHF events. Multiple trial protocols explicitly exclude CHF patients.
Sustained IGF-1 elevation may theoretically promote tumor growth. Multiple trial protocols exclude patients with active or recent malignancy.
MK-677 consistently decreases insulin sensitivity and raises fasting glucose. Multiple trial protocols exclude diabetic patients or require stringent glucose monitoring.
GH/IGF-1 elevation can worsen carpal tunnel symptoms. Excluded in several trial protocols.
No safety data in pregnancy or breastfeeding. All trial protocols exclude pregnant/nursing women.
LUM-201 Phase 3 (NCT06948214) and fibromyalgia trial (NCT00116129) explicitly exclude patients on strong CYP3A4 inhibitors/inducers, suggesting CYP3A4-mediated metabolism.
Talk to Your Doctor
Before considering MK-677 (Ibutamoren), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-8]
Evidence Assessment
MK-677 has been studied in multiple Phase I/II clinical trials (total ~1,700 subjects) with consistent surrogate endpoint improvements (GH, IGF-1, fat-free mass) but no robust clinical outcome benefits. The two largest completed trials were negative or terminated early: Phase 2 Alzheimer's trial (n=563, PMID: 19015485) showed no clinical benefit, and Phase IIb hip fracture trial (n=123, PMID: 21067829) was terminated early due to CHF signals. A Phase 3 trial (LUM-201/ibutamoren, NCT06948214, Lumos Pharma) for pediatric GHD is currently recruiting. Tier 3 reflects substantial Phase II human data with a Phase 3 in progress but no Phase 3 results or approvals
1Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trialNCT00474279PMID 18981485
Nass R, Pezzoli SS, Oliveri MC, et al. - Annals of Internal Medicine (2008) - Randomized, double-blind, placebo-controlled crossover (Phase I/II) - 65 (healthy elderly, age -¥60)
12-month MK-677 (25 mg/day): GH/IGF-1 restored to young adult levels. FFM +1.1 kg (95% CI 0.7-1.5) vs -0.5 kg placebo (p<0.001). No strength or functional improvement. Increased fasting glucose and decreased insulin sensitivity.
Limitations: Small sample. Surrogate endpoints only. No strength gains despite FFM increase.
2Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trialNCT00074529PMID 19015485
Sevigny JJ, Ryan JM, van Dyck CH, et al. - Neurology (2008) - Phase 2 RCT - 563 (mild-moderate Alzheimer's)
12-month MK-677: IGF-1 +73% but no significant differences on CIBIC+, ADAS-Cog, ADL, CDR. Negative trial.
Limitations: Demonstrates IGF-1 elevation alone does not translate to AD clinical benefit.
3MK-0677 for hip fracture recovery: Phase IIb studyNCT00128115PMID 21067829
Adunsky A, Chandler J, Heyden N, et al. - Archives of Gerontology and Geriatrics (2011) - Phase IIb RCT - 123 enrolled (83 actual, terminated early)
IGF-1 +51 ng/mL. Gait speed improved (+0.7, p=0.011) but stair climb NS. Trial terminated early due to CHF signals.
Limitations: Early termination. CHF safety signal in frail elderly. Small final sample.
4Stimulation of the GH-IGF-I axis by daily oral MK-677 in healthy elderlyPMID 8954023
Chapman IM, Bach MA, Van Cauter E, et al. - JCEM (1996) - Phase I/II RCT - 32 (healthy elderly)
4-week MK-677: GH +97% at 2 weeks, +82% at 4 weeks. IGF-1 restored to young adult levels. No tachyphylaxis.
Limitations: Short duration (4 weeks). Small sample. No body composition outcomes.
5MK-677, an orally active GH secretagogue, reverses diet-induced catabolismPMID 9467534
Murphy MG, Plunkett LM, Gertz BJ, et al. - JCEM (1998) - RCT (crossover) - 8 (healthy young men on caloric restriction)
MK-677 reversed nitrogen wasting induced by caloric restriction. Anti-catabolic properties demonstrated.
Limitations: Very small (n=8). Short-term. Healthy young men only.
6OraGrowtH Phase 3 Trial of LUM-201 in Children with GHDNCT06948214
Lumos Pharma (sponsor) - ClinicalTrials.gov (2025-2028 (recruiting)) - Phase 3 RCT - 150 (estimated, prepubertal children with GHD)
Currently recruiting. Primary endpoint: annualized height velocity at 12 months. Uses PEM strategy. No results yet.
Limitations: Not completed. First Phase 3 trial for ibutamoren.
7MK-0677 for FibromyalgiaNCT00116129
Bennett RM (PI), OHSU - ClinicalTrials.gov (2005-2008) - Phase 2 RCT - 64 (female fibromyalgia patients with low IGF-1)
Completed but results not formally published. Primary endpoint: FIQ score at 24 weeks.
Limitations: No published results available.
8Hepatotoxicity induced by MK-677PMID 40675653
Cobani E, et al. (2025) - Case report - 1
DILI with transaminitis after 2 months of MK-677 use. Resolved on discontinuation.
Limitations: Single case. Product purity not verified.