MK-677

MK-677 (ibutamoren) is a non-peptide, orally-active growth hormone secretagogue that selectively mimics the action of ghrelin, stimulating growth hormone (GH) and insulin-like growth factor 1 (IGF-1) secretion. Originally developed by Merck Research Laboratories, it increases GH secretion by up to 97% through activation of the ghrelin receptor, producing sustained elevations in IGF-1 levels comparable to those seen in younger adults. Clinical research has explored its potential applications in muscle wasting, osteoporosis, growth hormone deficiency, frailty, and age-related decline. While studies have demonstrated increases in lean body mass, bone turnover markers, and improved sleep quality, MK-677 remains an investigational drug without FDA approval. Safety concerns include increased risk of congestive heart failure in elderly populations, impaired insulin sensitivity, elevated fasting glucose levels, and fluid retention. It is currently banned by the World Anti-Doping Agency and listed as a prohibited dietary supplement ingredient by the U.S. Department of Defense due to its growth hormone-releasing properties and potential health risks.

Growth Hormone & IGF-1 Enhancement

• Sustained GH Elevation: MK-677 increases 24-hour mean growth hormone levels by 1.8-fold and serum IGF-1 levels by 1.5-fold in elderly subjects, restoring them to levels observed in healthy young adults ^[1][2]
• Long-Acting Oral Formula: Unlike peptide growth hormone secretagogues requiring injection, MK-677 provides convenient once-daily oral dosing with sustained activity ^[3]
• Peak GH Response: Single doses produce peak GH responses of 55.9 ± 31.7 μg/L, maintaining effectiveness at 22.6 ± 9.3 μg/L after one week of dosing ^[3]

Body Composition & Muscle Mass

• Lean Mass Gains: Clinical trials showed fat-free mass increased by 1.1 kg over 12 months in healthy elderly adults (ages 60-81), while placebo groups lost 0.5 kg ^[1]
• Reversal of Catabolism: MK-677 reversed diet-induced nitrogen wasting during caloric restriction, improving nitrogen balance from -1.48 g/day (placebo) to +0.31 g/day (treatment) ^[3]
• Muscle Preservation: Demonstrated potential for treating muscle wasting conditions by preventing protein breakdown during catabolic states ^[3]

Bone Health & Metabolism

• Increased Bone Turnover: Treatment with 25 mg/day for 8 weeks increased markers of bone formation by 23-28% within 2 weeks in obese young males ^[4]
• Enhanced Bone Density: In postmenopausal osteoporotic women, combination therapy with alendronate improved femoral neck bone mineral density by 4.2% compared to 2.5% with alendronate alone ^[5]
• Dual Bone Effects: MK-677 increases both bone formation and resorption markers, suggesting active bone remodeling ^[4][5]

Sleep Quality Enhancement

• REM Sleep Improvement: High-dose treatment increased REM sleep duration by approximately 50% in both young (18-30 years) and older adults (65-71 years) ^[6]
• Stage IV Sleep Extension: Young subjects experienced a 50% increase in stage IV (deep) sleep duration, with over 20% increase in REM sleep compared to placebo ^[6]
• Reduced Sleep Disruptions: Frequency of deviations from normal sleep patterns decreased from 42% under placebo to 8% with MK-677 treatment ^[6]
• Decreased REM Latency: Older adults showed significant reductions in time to enter REM sleep ^[6]

Age-Related Decline

• Functional Recovery: In hip fracture patients, gait speed improved significantly after 24 weeks of treatment (0.7-score difference, p = 0.011) ^[7]
• IGF-1 Restoration: Two weeks of treatment increased IGF-1 levels in elderly subjects to match those of younger adults in a dose-dependent manner ^[2]
• Potential Anti-Aging Effects: By restoring GH/IGF-1 axis function, may address multiple aspects of age-related physiological decline ^[1][2]

Clinical Safety Profile

• No FDA Approval: MK-677 remains an investigational new drug without approval for human consumption in the United States and is banned by WADA for athletic use ^[8]
• Early Trial Termination: A phase IIb hip fracture study was stopped early due to safety concerns, with MK-677 showing an "unfavorable safety profile" in elderly populations ^[7]
• Congestive Heart Failure Risk: FDA identifies MK-677 as posing "significant safety risks due to the potential for congestive heart failure in certain patients," with 4 cases in treatment groups versus 1 in placebo groups in elderly hip fracture patients ^[7][8]
• Metabolic Concerns: One case report documented new-onset diabetes in a 34-year-old bodybuilder after 26 days of use (blood glucose 27.5 mmol/L, HbA1c 102 mmol/mol) ^[9]

Regulatory Status

• Investigational Drug Status: Not approved for marketing or human consumption; companies selling products containing MK-677 have received FDA warning letters ^[8]
• Military Ban: Listed on Department of Defense Prohibited Dietary Supplement Ingredients List ^[8]
• Sports Prohibition: Banned by World Anti-Doping Agency as a growth hormone secretagogue ^[8]

Side Effects

• Glucose Metabolism: Significantly increases fasting blood glucose levels (from 5.4 to 6.8 mmol/L at 4 weeks) and decreases insulin sensitivity ^[1][9]
• Fluid Retention: Transient, mild lower extremity edema and swelling reported as common adverse effects ^[1]
• Increased Appetite: Most frequent side effect, though typically subsides within a few months of treatment ^[1]
• Musculoskeletal Symptoms: Muscle or joint pain reported in clinical trials ^[8]
• Other Effects: Numbness, nausea, diarrhea, anxiety, and potential negative impacts on bone mineral density despite increased bone turnover ^[8]
• Study Discontinuations: 8.2% of patients discontinued due to drug-related adverse events including hypertension (2 patients), fluid retention (2 patients), and hyperglycemia (3 patients) ^[9]

Research Gaps

• Long-Term Safety Unknown: Most clinical trials lasted 12-24 months; effects of prolonged use beyond 2 years remain unstudied
• Cardiovascular Risk Profile: The mechanism and full extent of heart failure risk, particularly in at-risk populations, requires further investigation
• Diabetes Risk: Whether MK-677 can trigger permanent insulin resistance or diabetes in predisposed individuals needs clarification
• Alzheimer's Disease: A 12-month trial with 563 patients found no benefit in slowing cognitive decline despite successfully elevating IGF-1 levels by 73% ^[10]
• Optimal Dosing: Limited data on dose-response relationships for specific therapeutic applications beyond the commonly studied 25 mg/day dose