MK-677 (ibutamoren) is an oral compound that signals the body to release more of its own growth hormone and raise IGF-1. It is not a true peptide - it is a small molecule that mimics ghrelin, and it is not approved as a supplement or wellness drug. Appetite increase, water retention, and rises in blood sugar are the major real-world concerns.
MK-677 is a non-peptide ghrelin-receptor (GHSR-1a) agonist and growth-hormone secretagogue. Human studies show it raises pulsatile GH, IGF-1, and IGFBP-3, and a 2-year randomized trial in older adults increased fat-free mass but found no strength or function benefit, with rising fasting glucose and reduced insulin sensitivity. Its translation is limited by mixed functional outcomes, metabolic adverse effects, investigational status, and anti-doping prohibition.
Ibutamoren / MK-677 is a small-molecule GHSR-1a agonist (free base C₂₇H₃₆N₄O₅S, 528.7 g/mol) that activates hypothalamic-pituitary ghrelin / GH-secretagogue signaling, enhancing endogenous pulsatile GH release and downstream IGF-1 / IGFBP-3 activity. Its strongest evidence supports somatotropic-axis pharmacodynamics rather than validated therapeutic protocols for longevity, performance, or body composition. In obese men, GH/IGF-1 rose but oral-glucose-tolerance testing showed impaired glucose homeostasis.
MK-677 sits in this atlas as the odd one out: a non-peptide small molecule that is nonetheless marketed and discussed alongside GH-secretagogue peptides. It has a genuinely stronger human trial base than most gray-market "research peptides," but that evidence supports pharmacodynamic effects (GH, IGF-1, fat-free mass, bone markers) rather than the wellness, longevity, or bodybuilding claims attached to it - and it carries real metabolic and regulatory caveats.
MK-677 works at a single switch - the ghrelin receptor - that tells the pituitary to release more growth hormone. From that one action flow its effects on IGF-1, appetite, water balance, blood sugar, and sleep.
All of MK-677's effects trace back to GHSR-1a agonism, which amplifies endogenous pulsatile GH and raises IGF-1/IGFBP-3. The downstream nodes - lean mass and nitrogen balance, bone turnover, sleep architecture - are real pharmacodynamic signals but vary in strength and clinical translation, and the same upstream switch drives the appetite, fluid, and glucose effects that limit it.
Mechanistically MK-677 is a potent, orally active, long-acting GHSR-1a agonist that mimics ghrelin's action on somatotroph cells, enhancing pulsatile GH secretion while preserving pulsatility better than exogenous GH. Receptor target and somatotropic pharmacodynamics are well established; several downstream effects are graded lower because functional endpoints remain incomplete.
MK-677 has no FDA-approved dosing protocol for wellness, bodybuilding, anti-aging, recovery, sleep, or clinic use. Adult research commonly used oral dosing - most often 25 mg once daily - but that is a research dose, not a consumer recommendation. Everything below is a research-model / hypothesis layer, not medical advice. Working unit: mg/day oral. Because MK-677 is oral and not injectable, the calculator below uses oral mg, capsule strength, and liquid concentration - not vial reconstitution.
5-10 mg PO once daily - a cautious extrapolation from practice-pattern logic, not an approved protocol.25 mg PO once daily is the best-documented adult research dose in older-adult and metabolic studies.5-10 mg PO once daily using a known mg/mL concentration.dose (mg) ÷ concentration (mg/mL) = mL to draw. Use the calculator below.| Band | Daily dose | ~mg/kg/day at 70 kg | Evidence basis | Grade |
|---|---|---|---|---|
| Low / cautious model | 5-10 mg/day | 0.071-0.143 | Conservative practice-pattern extrapolation; below most adult trial doses | D |
| Standard studied exposure | 20-25 mg/day | 0.286-0.357 | Adult human studies commonly used 25 mg/day | B |
| High / not preferred | >25 mg/day | >0.357 | Not needed for an Atlas default; higher dosing increases uncertainty and adverse-effect concern | D/P |
| Body weight | 10 mg/day | 15 mg/day | 20 mg/day | 25 mg/day |
|---|---|---|---|---|
| 55 kg | 0.182 | 0.273 | 0.364 | 0.455 |
| 65 kg | 0.154 | 0.231 | 0.308 | 0.385 |
| 75 kg | 0.133 | 0.200 | 0.267 | 0.333 |
| 85 kg | 0.118 | 0.176 | 0.235 | 0.294 |
| 95 kg | 0.105 | 0.158 | 0.211 | 0.263 |
| 105 kg | 0.095 | 0.143 | 0.190 | 0.238 |
Values are mg/kg/day. MK-677 is dosed as a fixed oral amount, not by weight; this table only shows how a fixed dose lands across body sizes. It is not a prescribing table.
| Trigger | Action | Rationale |
|---|---|---|
| Appetite increase, tolerable; no edema/glucose issue | Hold current dose | Appetite is common and may subside over time |
| New edema, rapid weight gain, hand numbness, or BP increase | De-escalate or hold | Fluid retention and edema are known concerns |
| Fasting glucose rises / insulin resistance worsens | Hold; reassess metabolic risk | Older-adult study showed fasting glucose rise and reduced insulin sensitivity |
| IGF-1 exceeds age-adjusted upper range | Hold / de-escalate | MK-677 can substantially raise IGF-1 |
| Active malignancy or unexplained tumor-marker concern | HARD STOP / avoid | GH/IGF-1 axis stimulation is mechanistically concerning |
| Competitive athlete subject to testing | HARD STOP / avoid | WADA-prohibited at all times |
| Pregnancy / lactation | HARD STOP / avoid | Safety not established |
| Severe untreated sleep apnea | Avoid or specialist-only | GH-axis agents and fluid retention may worsen airway/edema risk |
| Marker | Why track | Validated for MK-677 protocoling? |
|---|---|---|
| IGF-1 | Confirms GH/IGF-1 axis activation | Pharmacodynamic marker, not a dosing target |
| Fasting glucose | MK-677 may increase glucose | Monitoring supported, not an endpoint |
| Fasting insulin / HOMA-IR | Insulin sensitivity may worsen | Not validated for dose optimization |
| HbA1c | Longer-term glycemic risk | Not validated for MK-677 protocoling |
| Weight | Appetite, water retention, lean-mass change | Not validated; confounded by fluid |
| Blood pressure | Edema / fluid risk | Not validated |
| Edema exam | Known tolerability signal | Clinical monitoring, not a biomarker |
| Bone-turnover markers | Research signal in older adults | Research marker only |
Educational math only. MK-677 is oral - this calculator uses mg, capsule strength, and liquid mg/mL, not BAC-water vial reconstitution. MK-677 is not FDA-approved for consumer human use and is WADA-prohibited.
Fasting glucose, fasting insulin / HOMA-IR, HbA1c, IGF-1, blood pressure, weight, edema exam, sleep-apnea screen. Exclude active malignancy, uncontrolled diabetes, heart failure, pregnancy, and competitive-sport status.
Repeat fasting glucose and IGF-1. Hold if fasting glucose rises meaningfully or insulin sensitivity worsens; avoid pushing IGF-1 past the age-adjusted upper range.
Blood pressure, weight, and edema. Hold or de-escalate on rapid weight gain, new edema, hand numbness/paresthesia, or sustained BP rise.
HbA1c for longer-term glycemic trend; hold if the glycemic category worsens. Reassess whether any benefit justifies continued metabolic risk.
Periodic glucose/IGF-1, sleep-apnea symptoms, and appetite/weight. Long-term use is high-monitoring / research-only with no validated duration.
New or active malignancy concern, uncontrolled hyperglycemia, significant edema / heart-failure signs, worsening sleep apnea, pregnancy, or entry into a drug-tested competition.
MK-677's combinations are largely theoretical (Grade D/P) and dominated by one hard rule: do not stack it with other GH-axis agents. Because every partner that also raises GH/IGF-1 compounds the same edema, glucose, and IGF-1 liabilities, the engine treats GH/GHRP/GHRH co-administration as a constraint, not a synergy.
Treat the following as exclusion/avoidance conditions for MK-677 use or any stack: active malignancy or unexplained tumor-marker concern, uncontrolled diabetes, significant edema or heart-failure risk, untreated sleep apnea, pregnancy/lactation, pediatric use outside a specialist trial, and competitive-sport status (WADA-prohibited at all times). Do not combine MK-677 with other GH-axis agents outside specialist supervision - the risks are additive, and there is no validated benefit to doing so.
MK-677's safety profile is unusually well characterized for a "research" compound because controlled human trials exist. The dominant, repeatable signals are metabolic: increased appetite, mild edema, muscle pain, rising fasting glucose, and decreased insulin sensitivity. In obese men, glucose homeostasis was impaired on oral-glucose-tolerance testing despite GH/IGF-1 increases. The hard boundaries are malignancy, uncontrolled diabetes, heart failure/edema risk, untreated sleep apnea, pregnancy, and sport.
| Condition | Concern | Severity |
|---|---|---|
| Active malignancy / unexplained tumor concern | GH/IGF-1 axis stimulation may be undesirable | High |
| Uncontrolled diabetes | Glucose and insulin sensitivity may worsen | High |
| Severe insulin resistance / metabolic syndrome | Risk of impaired glucose handling | Moderate-High |
| Heart failure / significant edema | Fluid-retention risk | High |
| Untreated sleep apnea | Potential worsening via fluid/soft-tissue changes | Moderate-High |
| Pregnancy / lactation | Safety not established | High |
| Pediatric use outside a specialist trial | Investigational-only context | High |
| Competitive athlete | WADA-prohibited at all times | High |
| Severe renal / hepatic impairment | PK / safety uncertainty | Moderate-High |
| History of intracranial-hypertension symptoms | GH-axis agents raise concern in susceptible patients | Moderate |
Baseline, 4-8 weeks, then periodic. Hold if there is a clinically meaningful rise - the most important metabolic guardrail.
Baseline and 8-12+ weeks. Hold if the glycemic category worsens.
Baseline and 4-8 weeks. Avoid exceeding the age-adjusted upper range; confirms axis activation.
Baseline and periodic. Investigational; not validated as a dosing endpoint but useful for risk context.
Weekly early. Hold on sustained BP rise, rapid weight gain, or new edema.
Baseline and ongoing. Stop/evaluate if snoring or daytime sleepiness worsens.
MK-677 has a stronger human evidence base than most gray-market compounds: several randomized or controlled trials, including a 2-year study. The honest read is that this evidence supports pharmacodynamic effects - GH, IGF-1, IGFBP-3, nitrogen balance, fat-free mass, bone-turnover markers - not broad wellness, longevity, bodybuilding, or functional-performance claims, and the metabolic safety signal is clinically important.
In 65 healthy older adults, 25 mg/day MK-677 over up to 2 years increased fat-free mass but did not clearly improve function, and raised fasting glucose while reducing insulin sensitivity, with appetite, edema, and muscle pain reported. The most-cited and longest human trial.
Daily oral MK-677 stimulated the GH-IGF-1 axis in healthy elderly subjects, raising pulsatile GH and IGF-1 toward ranges seen in younger adults. Established the core pharmacodynamic effect.
Two months of oral MK-677 produced sustained GH, IGF-1, and IGFBP-3 increases but impaired glucose homeostasis on oral-glucose-tolerance testing - the clearest demonstration of the glucose trade-off.
Oral 25 mg MK-677 improved nitrogen balance during diet-induced catabolism and was generally tolerated short term. Supports the anabolic/nitrogen-retention signal without proving functional benefit.
MK-677 increased markers of bone turnover in elderly adults, and prolonged oral treatment improved sleep-quality parameters in young and older subjects. Both are real but limited signals, not validated indications.
In a pediatric GH-deficiency trial, the GHSR agonist LUM-201 elicited greater GH responses than standard secretagogues, supporting a stratified development path; earlier work showed oral ibutamoren mesylate raised GH, IGF-1, and IGFBP-3 in some children with GH deficiency.
MK-677's human evidence is Grade B and consistent for pharmacodynamics: it raises pulsatile GH, IGF-1, and IGFBP-3, improves nitrogen balance, increases fat-free mass, and increases bone-turnover markers. What it does not show is functional translation - the 2-year RCT found no clear strength or function benefit despite more fat-free mass - and a separate human trial found no clinical benefit on Alzheimer's progression. The metabolic safety signal (glucose, insulin sensitivity, edema, appetite) is clinically important, and the regulatory and sport restrictions are page-level warnings. Net: a genuine GH/IGF-1 pharmacology with weak outcome evidence and meaningful metabolic cost.
| Study | Design / population | Route / dose | Outcome | Grade |
|---|---|---|---|---|
| Chapman 1996 | Healthy elderly | Oral 10-25 mg | Increased pulsatile GH and IGF-1 | B |
| Chapman 1997 | GH-deficient adults | Oral MK-677 | Stimulated GH/IGF-1 axis | B |
| Murphy 1998 | Diet-induced catabolism | Oral 25 mg | Improved nitrogen balance | B |
| Svensson 1998 | Healthy obese males, 2 mo | Oral MK-677 | GH/IGF-1 up; impaired glucose on OGTT | B |
| Murphy 1999 | Elderly adults | Oral MK-677 | Increased bone-turnover markers | B |
| Bach 2004 | Hip-fracture recovery | Oral MK-0677 | IGF-1 up; function benefit uncertain | B |
| Nass 2008 | Older adults, RCT 2 yr | Oral 25 mg | FFM up; glucose up; insulin sensitivity down | B |
| Codner 2001 / LUM-201 2022 | Children with GHD | Oral | GH/IGF-1 response; investigational pediatric path | B |
| Study | Model | Finding | Grade |
|---|---|---|---|
| Lee 2018 | Rats | Oral MK-677 increased GH peaks; somatic-growth effects evaluated | C |
| Somatic-growth study 2018 | Rats | Effect of oral MK-677 on somatic growth | C |
| Jeong 2018 | Alzheimer's model | GHSR activation reduced amyloid/inflammation signals in model systems | C/P |
| GHS reviews | Translational | Summarize GHS-receptor biology and therapeutic possibilities and safety | P/D |
MK-677 is the only orally active, non-peptide member of this group - its selling point and its category quirk. The peptide comparators act by injection at the same axis (ghrelin-receptor GHRPs) or one step upstream (GHRH analogues); tesamorelin is the only FDA-approved comparator, which makes it the regulatory benchmark.
| Feature | MK-677 / Ibutamoren | Ipamorelin | CJC-1295 / Sermorelin | Tesamorelin |
|---|---|---|---|---|
| Class | Non-peptide ghrelin-receptor agonist | Peptide GHRP | GHRH analogues | GHRH analogue |
| Primary mechanism | GHSR-1a agonism → GH/IGF-1 | GH-secretagogue receptor; GH pulse | GHRH receptor → GH release | GHRH receptor activation |
| Evidence tier | Human B-level pharmacodynamic trials | Smaller human / practice base | Variable; sermorelin has historical clinical use | Approved-label evidence (HIV lipodystrophy) |
| Route | Oral | Injection | Injection | Injection |
| Regulatory status | Investigational; not FDA-approved; WADA banned | Not FDA-approved for broad use; WADA banned | Compounded / off-label; WADA banned | FDA-approved for a specific indication; WADA banned |
| Key advantage | Oral; once-daily; preserves pulsatility | Selective GH pulse, low cortisol effect | Amplifies GH via GHRH side | Regulatory-grounded, label evidence |
| Key limitation | Glucose/insulin, edema, appetite; banned in sport | Injectable; limited large trials | Injectable; variable evidence | Injectable; narrow approved indication |