MK-677
Ibutamoren, MK-0677, L-163, 191, Ibutamoren mesylate
Checked Oct 28, 2026
The short answer
Human-trial signal for muscle and body composition in healthy older adults
Grade B for muscle and body composition in healthy older adults, with a mixed result: a 2-year placebo-controlled trial found more lean mass (1.1 kg versus a 0.5 kg loss) but no gain in strength or function.
- Approved?
- Not approved for any use.
- Safety: E, flagged
- A hip fracture trial was stopped early for a heart failure signal, a 2-year trial in healthy older adults found higher fasting glucose and lower insulin sensitivity, and cancer risk over long use is untested.
The full answer: what it is for, the dose, the units
What people take it for: People take it for muscle and body recomposition, to raise growth hormone and IGF-1, and for sleep. It is not approved for any use in any country.
Does it work for muscle and body composition in healthy older adults? B, human-trial signal. Result: mixed.
Grade B for muscle and body composition in healthy older adults, with a mixed result: a 2-year placebo-controlled trial found more lean mass (1.1 kg versus a 0.5 kg loss) but no gain in strength or function. It reliably raises GH and IGF-1 (grade A, a lab marker), and its Alzheimer trial did not work.
No approval for any use.
Highest evidence for any use: A for raising growth hormone and IGF-1 blood levels (a lab marker, not a clinical benefit).
Safety: E, flagged. A hip fracture trial was stopped early for a heart failure signal, a 2-year trial in healthy older adults found higher fasting glucose and lower insulin sensitivity, and cancer risk over long use is untested.
Do not use if: Active or history of cancer (IGF-1 elevation is a hard contraindication).
Could it be placebo? The IGF-1 rise is a measured blood result that beat placebo in several trials, but for muscle, strength or function the one controlled trial shows no strength or function gain, and for sleep the only controlled data are 14 people over 7 to 14 days.
The dose people use, and the units to draw
There is no label dose; published trials used 25 mg by mouth once daily for 6 months to 2 years, and a 10 mg dose was tested for 2 weeks.
| Source | Dose | How often and how | Who it was for | Link |
|---|---|---|---|---|
| Chapman et al., J Clin Endocrinol Metab 1996 | 2 mg, 10 mg and 25 mg (three arms versus placebo) | Once daily by mouth, two study periods of 14 and 28 days | 32 healthy adults aged 64 to 81 | Abstract: GH rose dose-dependently; 25 mg/day restored IGF-I to young-adult levels |
| Copinschi et al., Neuroendocrinology 1997 | 5 mg and 25 mg in 8 young adults; 2 mg then 25 mg in 6 older adults | Once daily at bedtime for 7 days (young, crossover) or 14 days per period (older) | 8 healthy adults aged 18 to 30 and 6 adults aged 65 to 71 | Abstract: Methods and Results |
| Murphy et al. (MK-677 Study Group), J Bone Miner Res 1999 | 5, 10 and 25 mg; one study gave 25 mg then 50 mg | Once daily by mouth for 2 to 9 weeks across three randomized trials | 187 adults aged 65 or older, healthy or functionally impaired | Abstract: Methods and Results |
| Nass et al., Ann Intern Med 2008 | 25 mgUse this dose | Once daily by mouth for 2 years versus placebo (modified crossover) | 65 healthy adults aged 60 to 81 | Abstract: Intervention |
| Sevigny et al., Neurology 2008 | 25 mgUse this dose | Once daily by mouth for 12 months versus placebo | 563 people with mild to moderate Alzheimer disease | Abstract: Methods |
| Adunsky et al., Arch Gerontol Geriatr 2011 | 25 mgUse this dose | Once daily by mouth for 24 weeks versus placebo (terminated early) | 123 elderly hip fracture patients | Abstract: Methods and Results |
| ClinicalTrials.gov NCT05364684 (results posted) | 25 mgUse this dose | Once daily by mouth for 6 months, open label, single arm | 12 adults with BMI 25 or more and fatty liver | Arm description and primary outcome |
Trials ranged from 2 mg (Chapman 1996; Copinschi 1997) and 5 mg (Copinschi 1997; Murphy 1999) up to 50 mg for 2 weeks (Murphy 1999), with 25 mg once daily as the dose in every long trial (Nass 2008; Sevigny 2008; Adunsky 2011; NCT05364684).
Earlier community ranges, titration, cycling and split-dosing figures on the site had no named non-seller source and are removed. We found no MK-677 dose statement from Examine, Peter Attia, Huberman Lab or Dr. Abud Bakri that we could open and read. Merck's MK-677 label does not exist because the drug was never approved.
Reported by the named source, never prescribed by us.
How many units do I draw?
MK-677 is taken by mouth, so no syringe units are needed; the calculator is for injectable vials (units equal dose in mg divided by mg per mL, times 100 for a U-100 syringe). Open the dose calculator
Why it might work
- Oral absorption and GHSR-1a bindingMK-677
- Dual somatotroph and hypothalamic activationGHSR-1a binding triggers a Gaq-protein
- Pulsatile GH elevation with maintained 24-hour tonic levelUnlike injected recombinant GH (which
- Hepatic IGF-1 synthesis and downstream effects (assumed)Circulating GH reaches the liver and s
Assumed pathway, not shown in people.
MK-677 is a non-peptide agonist of the ghrelin receptor (GHSR-1a). By mimicking ghrelin, it stimulates the pituitary to release growth hormone in a pulsatile pattern, which then drives hepatic IGF-1 production. Unlike exogenous GH injections, MK-677 preserves the pulsatile nature of secretion rather than producing a flat pharmacological level. This is assumed to be safer than supraphysiologic GH injection, though no long-term comparative human data exists to confirm that assumption. Mechanism is well-characterized in humans. Clinical benefit translation is the open question.
The trials, claim by claim
Result tags: the Alzheimer claim is graded B because a 563-person randomized trial exists and tagged did not work; the extended-safety claim is graded B for the same reason. The FDA committee vote is a regulatory status, not an evidence grade.
- This is one of the most evidence-backed research compounds in this space. Multiple human RCTs confirm it raises GH and IGF-1 reliably, which is more than most peptides can say.
- The lean mass gains in elderly subjects are real but modest (roughly 1 kg over a year), and no trial has ever shown improvement in strength or function to go with them.
- Merck ran the trials and then did not pursue approval. The hip fracture study was stopped early for a congestive heart failure signal. That is not a footnote, that is the headline.
Raises IGF-1 and GH to young-adult ranges in older adults
Result: worked
Nass et al. 2008 (2-year RCT, n=65, age 60-81): confirmed GH secretion restored to young-adult levels; fat-free mass increased. Chapman et al. 1996 (PMID 8954023): dose-dependent GH and IGF-1 elevation in healthy elderly subjects. Effect is well-replicated across multiple trials.
Nass et al., Annals of Internal Medicine 2008 (PMID 18981485)Increases lean body mass in elderly or deconditioned patients
Result: mixed
Nass 2008 showed fat-free mass gains (+1.1 kg versus -0.5 kg at one year) without functional improvement, and the Adunsky hip-fracture trial improved gait speed but not most other functional measures. Lean mass rose in elderly volunteers; the functional payoff is not established.
Nass et al., Annals of Internal Medicine 2008 (PMID 18981485)Increases bone turnover markers
Result: worked
Murphy et al. (MK-677 Study Group) 1999 (PMID 10404019): 9-week pooled analysis (n=187 elderly adults across three RCTs) showed a 29% increase in serum osteocalcin and 10% increase in bone-specific alkaline phosphatase vs. placebo. Whether this improves bone density or fracture risk was not established.
Murphy et al. (MK-677 Study Group), Journal of Bone and Mineral Research 1999 (PMID 10404019)Slows or reverses Alzheimer's disease progression via IGF-1
Result: did not work
Sevigny et al. 2008 (PMID 19015485): 563 patients with mild-to-moderate AD, 12-month RCT. IGF-1 rose 73% at 12 months but there was zero effect on disease progression. Animal data supported the mechanism; human trial refuted the clinical endpoint.
Sevigny et al., Neurology 2008 (PMID 19015485)Is safe for extended use in healthy adults
Result: did not work
The only long-term trial in healthy adults (Nass 2008, 2 years) reported mostly mild side effects but a rise in fasting glucose and a fall in insulin sensitivity. Adunsky hip fracture trial (123 patients) was terminated early because of a heart-failure safety signal in a limited number of patients. Across trials: consistent worsening of insulin sensitivity, elevated cortisol, peripheral edema (reported as common, no rate sourced), and water retention. Merck discontinued development and the compound has no approved human use anywhere.
Adunsky et al., Arch Gerontol Geriatr 2011, phase IIb hip fracture trial (PMID 21067829)In a 12-person open-label pilot, 6 months of ibutamoren 25 mg daily did not significantly change liver fat in adults with fatty liver.
Result: did not work
Registry results only, single arm with historical controls, p=0.4; adverse events included increased appetite (7/12) and hyperglycemia (4/12).
ClinicalTrials.gov NCT05364684, results posted 2026-01-06FDA's advisory committee voted 13 to 1 against adding ibutamoren to the 503A bulks list in October 2024.
Regulatory fact from final summary minutes. It goes on the access axis, not a grade, and says nothing about efficacy.
FDA final summary minutes, PCAC Oct 29, 2024Risks and the label warnings
Adverse events
Documented in RCTs: insulin resistance (consistent across trials, worsens fasting glucose), peripheral edema (common), increased appetite with significant weight gain, elevated cortisol, joint pain, numbness and tingling. Serious: congestive heart failure signal in elderly patients with underlying cardiac vulnerability (Adunsky Phase IIb trial, led to early termination). FDA cites congestive heart failure as the safety risk behind its Category 2 listing. In a 12-person open-label fatty-liver pilot (25 mg daily for 6 months, results posted 2026), 7 reported increased appetite and 4 hyperglycemia. Single case reports describe raised liver enzymes (2025) and a splenic rupture alongside a SARM (2026), both confounded.
Contraindications
Active or history of cancer (IGF-1 elevation is a hard contraindication). Pre-existing insulin resistance or type 2 diabetes (worsens glycemic control). Congestive heart failure or structural heart disease. Children and adolescents (growth plate risk). Pregnancy.
Theoretical concerns
Sustained IGF-1 elevation raises theoretical concern for tumor promotion. IGF-1 receptor signaling drives cell proliferation; epidemiological data associates chronically elevated IGF-1 with increased risk of breast, prostate, and colorectal cancers. No MK-677 trial was large enough or long enough to assess cancer incidence, so this risk is unquantified not disproven.
What nobody knows yet
Long-term safety beyond 2 years in any population is not established. Cancer risk over multi-year use in healthy adults is completely unknown. The compound has no approved human use anywhere, reflecting the absence of a regulatory safety clearance. Interaction with TRT, exogenous GH, or GLP-1 agonists is not studied. Purity and dosing accuracy of black-market and research-chemical supply is unverified.
What else could explain the result
Commonly stacked with TRT (testosterone), SARMs, or anabolic steroids, making it impossible to attribute lean mass or recovery improvements to MK-677 alone. Also stacked with GLP-1 agonists (tirzepatide, semaglutide) for body recomposition, where appetite suppression from the GLP-1 offsets MK-677's known hunger drive. Baseline GH deficiency (which increases with age) makes elderly subjects respond more dramatically than young healthy adults, inflating perceived effect size when community reports skew older.
Is the vial what it says?
Cross-checked against the cited sources below. The Chapman 1996 citation is PMID 8954023; the Alzheimer trial is Sevigny et al., published November 2008; the osteocalcin rise is approximately 29% (Murphy 1999, 29.4%). The heart-failure signal and the sponsor's decision not to pursue approval are described in the risk section.
Half-life and storage
Half-life: Approximately 24 hours. One of the longest half-lives of any GHS compound, which is why adverse effects (appetite, water retention, cortisol) persist continuously rather than episodically.
Once mixed: N/A. MK-677 is an oral tablet or capsule, not a reconstituted peptide. No injection or mixing required. Degradation risk is from heat, moisture, and light like any oral compound. Research-chemical supply quality is the primary purity concern.
What I noticed, and what people report
What people report
Volume of reports: strong. Large, consistent community + practitioner record.
Very high. MK-677 has one of the largest community footprints of any research compound. Widely discussed on bodybuilding forums and in performance communities for 15+ years.
Moderately consistent on the subjective effects (vivid dreams, hunger spike, water retention, improved sleep quality as reported). Inconsistent on lean mass results, which likely reflects the confound of stacking and variable diets.
Mixed to moderate. The anecdotal effects (hunger, water retention, sleep changes) align with the known mechanism. The body recomposition claims are less credible given that trials in controlled settings showed modest lean mass gains without strength improvements.
- Anecdote: extremely strong hunger, especially for carbohydrates, within 1-2 hours of dosing and persisting all day. Users report this is the hardest side effect to manage on a cut.
- Anecdote: vivid, intense dreams reported almost universally. Often the first subjective sign that the compound is active. Consistent with increased slow-wave sleep documented in trials.
- Anecdote: noticeable water retention and puffiness (face and extremities) within the first 1-2 weeks, often mistaken for muscle gain. Most users report it partially resolves after week 3-4.
- Anecdote: joint comfort often improves, especially in users with pre-existing tendon issues. Attributed to IGF-1 effects on connective tissue, though no controlled trial has isolated this outcome.
Reports are anecdote, not proof.
Can you tell if it is working?
Yes, blood IGF-1 confirms it's active and a CGM reliably catches the glucose downside; DEXA fat-free mass is the nearest thing to an efficacy signal but is heavily confounded by water, and no non-blood channel proves a functional benefit.
Bloodwork
A routine lab actually tracks whether this is working.
MK-677 (ibutamoren) is an orally active ghrelin-receptor (GHSR-1a) agonist that amplifies endogenous pulsatile GH release; GH drives hepatic IGF-1 production, so serum IGF-1, a standard LabCorp/Quest test, rises measurably. The rise reflects the drug's biological action on the GH axis, not merely that the compound is present.
IGF-1 climbs into the upper part of the age-adjusted reference range; in trials daily MK-677 restored older adults' IGF-1 toward the young-adult range within roughly 2-4 weeks. A clear rise above your own pre-dose baseline is the readout.
GHSR-1a agonism amplifies GH pulses, and GH drives hepatic IGF-1 output; IGF-1 is the standard, well-validated blood proxy for GH-axis stimulation in humans, demonstrated specifically for MK-677 in RCTs.
Modest rise above baseline, tracking the IGF-1 increase. Confirmatory only.
IGFBP-3 is GH-dependent and moves with IGF-1, so a concordant rise corroborates GH-axis stimulation; it shifts less dramatically than IGF-1 and is not needed if IGF-1 is drawn.
Draw baseline
Draw IGF-1 before the first dose (single serum IGF-1; time of day is not critical since IGF-1 is stable day-to-day).
Retest
4-8 weeks. IGF-1 often begins rising within 1-2 weeks and plateaus by ~2-4 weeks, so a 4-8 week retest reliably captures the steady-state effect.
Read this before you spend on labs
IGF-1 confirms the GH axis is genuinely stimulated, but it does NOT prove downstream benefit (lean mass, sleep, recovery, appetite), those can lag or fail to materialize even with a good IGF-1 bump. Separately, order a CMP/fasting glucose (add HbA1c for use beyond ~8-12 weeks): MK-677 reliably raises fasting glucose and lowers insulin sensitivity, so track these as a SAFETY signal, not as evidence it is 'working.' Anyone with insulin resistance or T2D should be cautious.
- Chapman IM et al., J Clin Endocrinol Metab 1996, daily oral MK-677 restored IGF-1 to the young-adult range in healthy elderly (PMID 8954023)
- Nass R et al., Ann Intern Med 2008, 2-yr RCT: MK-677 increased GH and IGF-1 to young-adult levels, raised fat-free mass; noted higher fasting glucose / lower insulin sensitivity (PMID 18981485)
Other ways to track it
14-day continuous glucose monitor (Dexcom/Libre), mean glucose, fasting/morning glucose, and glucose variability/time-in-range; corroborate with a lab HbA1c
A rise in mean and fasting glucose with reduced insulin sensitivity is one of the most RELIABLE objective signals that MK-677 is pharmacologically active, the Nass RCT showed fasting glucose +~5 mg/dL (P=0.015), HbA1c +0.2% (P=0.002), and worsened insulin sensitivity (QUICKI, P<0.001). Frame this honestly: it confirms the drug is working on you, but it is a metabolic DOWNSIDE and safety signal, not a benefit. A CGM turns that abstract risk into a number you can watch and act on.
GH secretagogue-driven GH elevation is counter-regulatory to insulin, reliably raising fasting glucose and reducing insulin sensitivity, a direct, dose-dependent pharmacodynamic effect a CGM measures continuously.
DEXA whole-body scan, fat-free (lean) mass, total fat mass, and visceral adipose tissue (VAT); pair with femoral-neck/spine bone density
A working result shows a real rise in fat-free mass, in the 2-year Nass RCT lean mass rose ~1.6 kg relative to placebo (P<0.001). Honest caveat: a large share of that 'lean' is intracellular water and glycogen (mild edema occurred in ~44% of users), and in the trial strength and physical function did NOT improve, so a DEXA lean-mass bump is not proof of new contractile muscle, this is why it rates as a partial, not direct, efficacy readout. Do NOT expect a VAT drop, unlike tesamorelin, MK-677 did not reduce visceral fat (CT-measured, P=0.68), and total fat mass trended up (P=0.13). Watch bone: femoral-neck density fell slightly versus placebo (P=0.004).
MK-677 is a ghrelin-mimetic GH secretagogue; sustained GH/IGF-1 elevation drives fluid retention and modest lean/fat-free-mass accrual, which DEXA quantifies, but because much of that mass is water and it does not translate to strength, DEXA confirms activity more than benefit. It does not mobilize visceral fat the way GHRH analogs like tesamorelin do.
Home scale (weight trend) + waist circumference + a visual/finger-press edema check on ankles and hands
Expect a fairly quick jump in scale weight, the RCT showed +2.7 kg vs +0.8 kg placebo (P=0.003), plus possible puffiness/edema and waist increase. Read this honestly: it is largely water retention and appetite-driven intake, NOT muscle, and is easily mistaken for muscle gain. Its value is as a cheap corroborator: rapid weight-up with edema confirms the drug is acting, and pairs with DEXA to separate water from tissue. A stalling or falling weight during a bulk suggests under-dosing or non-response.
GH-secretagogue fluid retention plus the strong ghrelin-driven appetite (especially for carbohydrates) reliably add body water and intake, producing prompt, objective weight and girth changes that a scale and tape capture.
Oura or WHOOP, deep (slow-wave) sleep minutes and REM minutes, tracked with a multi-week baseline
Some users may see an uptick in deep-sleep and/or REM minutes; a polysomnography study (Copinschi 1997) found increased slow-wave and REM sleep. Be honest about the weakness: that human evidence is short-term lab PSG, longer-term benefit is unestablished, and consumer wearables estimate sleep stages imperfectly with high night-to-night noise, so a null or noisy result does NOT mean the compound is inactive. Vivid dreams are near-universal anecdotally but are subjective and not a wearable metric.
GH secretion is physiologically coupled to slow-wave sleep, and ghrelin-mimetic GH secretagogues appear to reinforce that coupling, plausibly increasing deep-sleep and REM time.
Bottom line
MK-677 is easy to confirm as pharmacologically active but hard to validate as beneficial. Blood IGF-1 (handled separately) and a CGM glucose rise are the most reliable objective confirmations it is 'doing something'; a DEXA lean-mass gain and prompt scale-weight/water gain corroborate activity but are heavily confounded by water. The clean efficacy wins seen with other compounds are absent here: no visceral-fat reduction (unlike tesamorelin), no proven strength or functional improvement, a slight bone-density dip, and only weak, noisy wearable-sleep support. The strongest signals (IGF-1, higher glucose, appetite, water weight) are as much side-effect as benefit, so track it, but interpret any positive DEXA or weight change conservatively, because none of these readouts proves a durable clinical benefit.
Logging baseline vs retest is the whole game. The Truth Tracker is our free log for bloodwork, DEXA, genetics, and wearable data, bring your own numbers.
How to track itHistory
First documented human use: 1996. Chapman et al. published oral administration data in healthy elderly subjects in the Journal of Clinical Endocrinology and Metabolism, confirming GH and IGF-1 elevation with daily dosing.
- 1996Chapman et al. published the first human trial showing oral MK-677 stimulates GH and IGF-1 in healthy elderly subjects (Journal of Clinical Endocrinology and Metabolism, PMID 8954023). Merck was the developer.
- 2008Nass et al. published the 2-year RCT in Annals of Internal Medicine (PMID 18981485). Confirmed GH restoration and lean mass gains but failed to show functional improvement. Worsened insulin sensitivity documented.
- 2008Sevigny et al. published the 563-patient Alzheimer's trial in Neurology (PMID 19015485, published November 18, 2008). Despite raising IGF-1 by 73%, MK-677 had no clinical effect on disease progression. Major blow to the cognitive-benefit hypothesis.
- 2011Adunsky et al. Phase IIb hip fracture trial terminated early because of a heart-failure safety signal in a limited number of patients. Merck ultimately did not pursue FDA approval. Compound became a research chemical used off-label.
- May 2026Another sponsor (Lumos Pharma) begins a Phase 3 trial of the same molecule, as LUM-201, in children with growth hormone deficiency (NCT06948214). Still no approval anywhere.
All sources
- Nass et al. 2008, Annals of Internal Medicine (PMID 18981485), 2-year RCT, primary evidence anchor(65 healthy older adults, 2-year double-blind crossover. Confirmed GH/IGF-1 restoration and lean mass gains but no functional improvement and worsened insulin sensitivity.)
- Sevigny et al. 2008, Neurology (PMID 19015485), largest single MK-677 RCT (n=563).(Alzheimer's disease trial. Confirmed target engagement (IGF-1 +73%) but zero clinical benefit on disease progression. Showed the mechanism does not reliably translate to clinical endpoints.)
- Chapman et al. 1996, Journal of Clinical Endocrinology and Metabolism (PMID 8954023), first GH/IGF-1 human data(Established oral bioavailability and dose-dependent GH secretion in healthy elderly subjects (64-81 years). The foundational human pharmacology paper. Previously mislabeled in this file as PMID 9467534, which is a different study (Murphy et al. 1998, diet-induced catabolism in 8 young adults).)
- OPSS (Operation Supplement Safety) MK-677 profile, U.S. military safety resource(Summarizes regulatory status, adverse event profile, and the rationale for why MK-677 is not approved. Useful non-industry reference.)
- Adunsky et al., Arch Gerontol Geriatr 2011, phase IIb hip fracture trial (PMID 21067829)(Primary source for the heart-failure signal: the trial was terminated early; the abstract reports a limited number of patients. Gait speed improved; most other functional measures did not.)
- ClinicalTrials.gov NCT05364684, results posted 2026-01-06(12-person open-label fatty-liver pilot of ibutamoren 25 mg daily for 6 months; no significant change in liver fat.)
- ClinicalTrials.gov NCT06948214, Phase 3 pediatric growth hormone deficiency (LUM-201)(Same molecule under another sponsor, started May 2026. Not a consumer route.)
- FDA final summary minutes, PCAC Oct 29, 2024(Advisory committee voted 13 to 1 against listing ibutamoren for 503A.)
- Chapman IM et al. Stimulation of the growth hormone-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab 1996;81:4249-57. PMID 8954023(dose table)
- Copinschi G et al. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology 1997;66:278-86. PMID 9349662(dose table)
- 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;14:1182-8. PMID 10404019(dose table)
- Nass R et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008;149:601-11. PMID 18981485(dose table)
- Sevigny JJ et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology 2008;71:1702-8. PMID 19015485(dose table)
- Adunsky A et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture. Arch Gerontol Geriatr 2011;53:183-9. PMID 21067829(dose table)
- ClinicalTrials.gov NCT05364684, The Impact of Ibutamoren on Nonalcoholic Fatty Liver Disease(dose table)
Not medical advice. Grades reflect the evidence as of the date above and will change as data arrives. Reports from users are anecdote, not proof. Talk to a licensed clinician before you act on anything here.