MK-677 (Ibutamoren)

MK-677 (Ibutamoren) is a growth hormone releaser that prompts the pituitary gland to release the body's own growth hormone by acting on the ghrelin (hunger hormone) receptor. Unlike most compounds here, it's taken orally, as a pill or liquid, and it isn't actually a peptide, it's a small-molecule drug. It's pursued for muscle, sleep, and anti-aging effects. A two-year trial in healthy older adults found it added lean (fat-free) mass, but strength and physical function did not improve, and a hip-fracture trial in older adults was stopped early because of heart failure in some patients, and its researchers concluded the drug's safety was unfavorable for that group. It's not FDA-approved for any use, it's banned in drug-tested sport, and it's now in Phase 3 trials for childhood growth hormone deficiency.

MK-677 (ibutamoren) is an oral compound studied to raise growth hormone and IGF-1. Early pharmacology showed daily oral MK-677 raised those hormones in healthy older adults. A two-year randomized trial in healthy older adults found fat-free mass increased, and so did body cell mass (the body's living, working tissue), but strength and physical function did not improve, though the trial was too small and too short to judge them well, and insulin sensitivity worsened. A Phase 2b trial in elderly hip-fracture patients was stopped early because of heart failure in some patients, and its researchers concluded the drug's safety was unfavorable for that group. The body-composition and sleep uses people pursue are not confirmed by trials proving those outcomes.

Not FDA-approved for any indication. Originally developed by Merck through phase 2 / phase 2b clinical trials in the late 1990s and 2000s for adult growth hormone deficiency, age-related frailty, hip fracture recovery, and Alzheimer's disease — none of which advanced to FDA approval. A multicenter, placebo-controlled phase 2b hip fracture trial (Adunsky 2011) was terminated early due to a safety signal of congestive heart failure in a limited number of patients, and its authors concluded MK-677 has an unfavorable safety profile in that population[³] — a safety signal that has materially shaped the regulatory and clinical context for MK-677. Currently under phase 3 development by Lumos Pharma (the OraGrowtH trial program in pediatric GHD) — if successful, would represent the first oral GH secretagogue to achieve FDA approval. Not DEA-scheduled. WADA-banned in regulated sport — explicitly listed as "ibutamoren (MK-677)" under Section S2.2.4 (Growth Hormone Releasing Factors → growth hormone secretagogues / GHS) of the 2026 and 2027 Prohibited Lists[¹⁰], the same subsection as Ipamorelin. Currently sold as a research compound (not a peptide; technically a small-molecule drug) outside the FDA-approved framework.

MK-677 is taken orally and is not a peptide. It is not FDA-approved, and a clinical trial was stopped early over a heart-failure safety signal; it also worsened insulin sensitivity in trials. It is banned in regulated sport (WADA Prohibited List, Section S2.2.4). VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ MK-677 is not FDA-approved for any indication and is currently under phase 3 development by Lumos Pharma for pediatric GHD. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ MK-677 is not a peptide. It is a small-molecule, non-peptide, spiropiperidine drug. This entry exists in the Vialwise library because researchers running peptide protocols frequently use MK-677 alongside peptide stacks (CJC-1295, Ipamorelin, etc.) — and because MK-677 acts on the same ghrelin receptor (GHS-R1a) as the peptide GHRP class (Ipamorelin, GHRP-2, GHRP-6). MK-677 is structurally a non-peptide oral drug; mechanistically a ghrelin receptor agonist. This is a different compound class from the peptides that dominate the rest of the Vialwise library. Researchers should be explicit with themselves about which compound class they are using.

⚠️ Important safety signal: congestive heart failure stopped the Adunsky 2011 phase 2b hip fracture trial early. A multicenter, randomized, placebo-controlled phase 2b trial in 123 elderly hip fracture patients (Adunsky et al., 2011) was terminated early due to a safety signal of congestive heart failure in a limited number of patients, and the authors concluded that MK-677 has an unfavorable safety profile in this patient population.[³] The signal comes from elderly patients recovering from hip fracture, but it is meaningful for any researcher considering MK-677, particularly those with cardiovascular risk factors. The Lumos Pharma OraGrowtH phase 3 program in pediatric GHD studies a different population (treatment-naive prepubertal children).

⚠️ Oral bioavailability — distinct from the peptide GHRPs. MK-677's non-peptide spiropiperidine structure confers resistance to proteolysis and enables efficient oral absorption. The published trials gave it by mouth once daily.[¹][²][³] This is a fundamental architectural difference from the injectable peptide GHRPs (Ipamorelin, GHRP-2, GHRP-6) covered elsewhere in this library — same receptor target, completely different molecule class and administration route. Researchers should not confuse MK-677 with the peptide GHRPs even though they share the GHS-R1a target.

MK-677 (ibutamoren mesylate; developmental codes MK-0677 / L-163,191) is a non-peptide spiropiperidine drug developed by Merck in the 1990s as an orally bioavailable growth hormone secretagogue. The molecule binds and activates the ghrelin receptor (GHS-R1a) at pituitary somatotrophs, mimicking the GH-stimulating effect of endogenous ghrelin. Its non-peptide spiropiperidine structure confers resistance to proteolysis and enables absorption when taken by mouth. It is taken once daily by mouth, unlike the injectable peptide GHRPs (Ipamorelin, GHRP-2).

Mechanism vs the peptide GHRPs. MK-677 and the peptide GHRPs (Ipamorelin, GHRP-2, GHRP-6, hexarelin) all bind the same ghrelin receptor (GHS-R1a) at pituitary somatotrophs and trigger the same GH-release pathway. The practical differences are route and dosing frequency: MK-677 is taken by mouth once daily; Ipamorelin and the peptide GHRPs are injected. In the cited studies MK-677 amplified the body's existing pulsatile GH release rather than replacing it with a continuous one. In healthy older adults, GH pulses grew taller and the levels between pulses rose, while the number of pulses did not change;[¹] the two-year trial likewise describes enhanced pulsatile GH secretion.[²] Downstream IGF-1 rose into the young-adult range in both studies.[¹][²] Both also recorded higher fasting glucose, and the two-year trial reported reduced insulin sensitivity.[¹][²] See the Ipamorelin entry for the injectable route.

Clinical development history. Merck advanced MK-677 through phase 2 / phase 2b development in multiple indications during the late 1990s and 2000s: - Healthy older adults (pharmacology) — Chapman 1996 (32 healthy adults aged 64–81, up to 4 weeks of daily dosing) showed oral MK-677 raised GH and IGF-1, restoring IGF-1 to young-adult levels [¹] - Age-related frailty / sarcopenia — Nass 2008 (Annals of Internal Medicine, n=65 healthy older adults, 2-year modified-crossover RCT with primary endpoints at 1 year MK-677 vs placebo) reported fat-free mass rising 1.1 kg with MK-677 versus a 0.5 kg fall with placebo, with body cell mass (as reflected by intracellular water) rising as well — but no change in strength or function, which the authors said the study was not powered to evaluate, and worsening of insulin sensitivity[²] - Hip fracture recovery — Adunsky 2011 phase 2b trial (n=123 elderly hip fracture patients) terminated early due to a safety signal of congestive heart failure in a limited number of patients; the authors concluded MK-677 has an unfavorable safety profile in this population[³] - Alzheimer's disease — Sevigny 2008 randomized trial in mild-to-moderate Alzheimer's reported no clinical effect on AD progression - None of these programs advanced to FDA approval. Merck wound down the elderly-population MK-677 program after the Adunsky 2011 safety signal.

Lumos Pharma OraGrowtH program (currently active phase 3). Lumos Pharma acquired the MK-677 program and is currently conducting a multicenter, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT06948214; recruiting, started 2026-05-20; n=150; randomized 2:1 LUM-201:placebo) in treatment-naive prepubertal children with growth hormone deficiency[⁵][⁶]. If successful, this would represent the first oral GH secretagogue to achieve FDA approval. The pediatric GHD population is regulatorily distinct from the adult elderly-frailty population — children with GHD have a different cardiovascular risk profile, and the OraGrowtH program is the path being pursued to bring MK-677 to FDA approval. A 2025 review of new directions in pediatric growth hormone treatment (Stawerska) discusses preliminary data on oral ibutamoren in children with partial GHD, consistent with this program's rationale.[⁹]

Regulatory status (US). MK-677 is not FDA-approved for any indication as of this entry's last-updated date. The Lumos Pharma phase 3 program is currently active. MK-677 is classified as an Investigational New Drug in the United States, meaning it is not legally available for general human use outside the FDA-approved clinical trial framework. Not DEA-scheduled. Research-community supply chains exist (oral capsules and powder formulations dispensed for "research use only" through compounding pharmacies and overseas suppliers) but operate outside the FDA-approved framework.

Regulatory status (sport — WADA). MK-677 is explicitly listed under Section S2.2.4 (Growth Hormone Releasing Factors → growth hormone secretagogues / GHS) of the 2026 and 2027 WADA Prohibited Lists[¹⁰], in the same subsection as Ipamorelin and other GHS-class compounds. Verbatim from the 2026 List (unchanged in 2027): "growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin]"[⁴] — MK-677 is named explicitly. Prohibited at all times in regulated sport.

Common research interests. Despite the absence of FDA approval and the Adunsky 2011 safety signal, MK-677 is widely used in research-community contexts for: - Body composition / anabolic effects — driven by sustained GH/IGF-1 elevation; the most common research-community use case - Sleep quality — MK-677 has been reported to increase REM sleep duration (20% in young subjects, 50% in older subjects in a small early study); sleep-quality improvement is one of the consistently reported subjective effects - Adjunct to peptide stacks — sometimes combined with Ipamorelin (despite same-receptor redundancy at the GHS-R1a target — see Stacks section), CJC-1295, or testosterone - Anti-aging / longevity contexts — driven by the original Merck adult-frailty-and-elderly-population development rationale

The Adunsky 2011 CHF safety signal is meaningful clinically but has not deterred research-community use; researchers using MK-677 should be explicit with themselves about cardiovascular risk profile, particularly with prolonged use or pre-existing cardiac risk factors.

Commonly reported

• Increased appetite (ghrelin-receptor-mediated) — the most consistently reported side effect. Dose-dependent: manageable for most users; can be intense ("hunger" within 1–2 hours of dosing). Most users report appetite normalization after 2–4 weeks as ghrelin receptor sensitivity adjusts; in others appetite stimulation persists.
• Water retention / mild edema — particularly in the first 1–2 weeks of dosing; typically resolves with continued use or mild dose reduction
• Insulin resistance / impaired glucose tolerance — well-documented in the Nass 2008 trial; HbA1c and fasting glucose elevation observable within 6–12 months of continuous use
• Mild fatigue or lethargy — particularly during initial dose escalation
• Sleep architecture changes — typically increased REM sleep duration; occasionally reported as more vivid dreams
• Mild myalgia or arthralgia — uncommon; consistent with the broader GH-axis side-effect profile

Serious

• New or worsening symptoms of congestive heart failure (peripheral edema with shortness of breath, exercise intolerance, paroxysmal nocturnal dyspnea) — given the Adunsky 2011 safety signal, MK-677 should be discontinued at the first sign of CHF symptoms, particularly in older patients or those with pre-existing cardiac risk
• New or worsening glucose intolerance / hyperglycemia
• Severe edema or symptoms suggestive of fluid overload
• New cardiovascular symptoms (chest pain, dyspnea, palpitations) — possible LV strain or arrhythmia
• Signs of liver stress (unusual fatigue, right-upper-quadrant pain, dark urine, jaundice) — a 2025 case report (Cobani et al.) described transaminitis in a healthy man after ~2 months of MK-677 that normalized after discontinuation; single-case evidence, but a reason to monitor liver enzymes on-cycle[⁷]
• Sudden severe abdominal pain — a single 2026 case report (Jaffry et al.) described spontaneous splenic rupture in a man using MK-677 together with the SARM RAD-140; the authors frame the compounds' role as speculative and the case is confounded by co-use, so this is a low-evidence signal only[⁸]
• Severe psychiatric changes (uncommon but reported with very high doses)

Strong contraindications / cautions:

Pre-existing congestive heart failure or significant cardiac vulnerability — strong caution per the Adunsky 2011 phase 2b CHF safety signal

Active malignancy — IGF-1 elevation may promote cancer progression

Diabetes / impaired glucose tolerance — caution; MK-677 worsens insulin sensitivity

Pregnancy and lactation — no data; default to contraindicated

Pediatric use (outside the Lumos Pharma OraGrowtH trial framework) — the active phase 3 program operates under specialist supervision in a controlled trial population; off-label pediatric use outside this framework is strongly contraindicated

Concurrent corticosteroid use — caution; corticosteroids may interfere with MK-677's GH-stimulating effect

Warnings:

Pregnancy and lactation: contraindicated (no human data).

Long-term safety in healthy adults is essentially unknown — no multi-year human safety dataset exists for the research-community continuous-use pattern.

Regulatory note (US): MK-677 is not FDA-approved; classified as an Investigational New Drug. Distribution outside the FDA-approved clinical trial framework is regulated under the broader compounding-pharmacy and "research use only" framework that applies to most non-FDA-approved compounds.

Regulatory note (sport): MK-677 / ibutamoren is explicitly listed in Section S2.2.4 of the WADA 2026 and 2027 Prohibited Lists[¹⁰] alongside Ipamorelin and other GHS-class compounds; prohibited at all times in regulated sport.[⁴]

Growth hormone secretagogue

A compound that signals the body to release its own growth hormone, rather than supplying growth hormone directly.

Ghrelin receptor

a receptor that, when activated, triggers growth hormone release and hunger.

Oral bioavailability

how well a drug is absorbed when taken by mouth rather than injected.

IGF-1

a growth factor the liver makes in response to growth hormone; used as a lab marker (and, for IGF-1 LR3, a growth factor that drives tissue and muscle growth).

WADA Prohibited List

The list of substances banned in regulated sport by the World Anti-Doping Agency.

1. Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO. (1996). Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. The Journal of Clinical Endocrinology and Metabolism, 81(12):4249–4257.(PMID 8954023)
2. Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE Jr, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9):601–611.(PMID 18981485)
3. Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA. (2011). MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Archives of Gerontology and Geriatrics, 53(2):183–189.(PMID 21067829)
4. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. MK-677 / ibutamoren is named explicitly under Section S2.2.4 (Growth Hormone Releasing Factors → growth hormone secretagogues / GHS). Verbatim from the 2026 List, page 8: "growth hormone secretagogues (GHS) and their mimetics [e.g. anamorelin, capromorelin, ibutamoren (MK-677), ipamorelin, lenomorelin (ghrelin), macimorelin and tabimorelin]". Prohibited at all times.
5. Lumos Pharma. A Multicenter, 12-Month, Randomized, Double-Blind, Placebo-Controlled Phase 3 Efficacy and Safety Study of Daily Oral LUM-201 (ibutamoren) in Naïve-to-Treatment, Prepubertal Children With Growth Hormone Deficiency (the OraGrowtH Phase 3 program). ClinicalTrials.gov: NCT06948214. Sponsor Lumos Pharma; status RECRUITING; start 2026-05-20; n=150; randomized 2:1 LUM-201:placebo; primary completion 2027-12. The active Phase 3 program that — if successful — would represent the first oral GH secretagogue to achieve FDA approval.(NCT06948214)
6. Lumos Pharma. OraGrowtH210 — Phase 2 study of oral LUM-201 (ibutamoren) in pediatric growth hormone deficiency (LUM-201 vs rhGH / Norditropin). ClinicalTrials.gov: NCT04614337. Sponsor Lumos Pharma; status COMPLETED 2024-09-04; n=104. Results first posted to ClinicalTrials.gov 2026-06-17.(NCT04614337)
7. Cobani E, et al. (2025). Hepatotoxicity induced by MK-677. BMJ Case Reports, 18(7):e265728.(PMID 40675653)
8. Jaffry K, et al. (2026). Spontaneous Splenic Rupture in a Patient With Recent Use of Performance-Enhancing Compounds. Cureus, 18(3):e106106.(PMID 42064485)
9. Stawerska R. (2025). New directions in growth hormone treatment in children. Pediatric Endocrinology, Diabetes and Metabolism, 31(4):143–154.(PMID 41693185)
10. World Anti-Doping Agency. World Anti-Doping Code International Standard Prohibited List 2027 (effective 1 January 2027). PDF: wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf. MK-677 (Ibutamoren) is named under S2.2.4: "ibutamoren (MK-677)".

• CJC-1295 — discussed together in this entry's stacks section
• Testosterone — discussed together in this entry's stacks section
• CJC-1295 / Ipamorelin Blend — same mechanism class
• GHRP-2 — same mechanism class
• GHRP-6 — same mechanism class
• Hexarelin — same mechanism class