Sermorelin + MK-677 (Ibutamoren) Stack: Safety and Monitoring Guide

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What sermorelin is and what it does

Sermorelin is a 29-amino-acid analogue of human growth hormone-releasing hormone, the shortest synthetic peptide with the full biological activity of GHRH, and it works by prompting the pituitary to release the body's own growth hormone. It is not growth hormone [10]. After an intravenous dose in healthy men it was eliminated quickly, yet growth hormone stayed raised for about 3 hours [11].

Sermorelin acetate was approved as Geref for two narrow uses: testing the pituitary's ability to secrete growth hormone (the 0.05 mg ampule, NDA 019863) and treating idiopathic growth hormone deficiency in children with growth failure (the 0.5 mg and 1 mg vials, NDA 020443) [1]. The manufacturer discontinued both products in 2008 and asked FDA to withdraw the applications; FDA withdrew approval of both effective June 18, 2009, and in March 2013 determined Geref was not withdrawn from sale for reasons of safety or effectiveness [1]. Geref was not approved for adults, anti-aging, weight loss or athletic performance [1]. Sermorelin sold in the US today is compounded, and compounded drugs are not FDA-approved: FDA does not review their safety, effectiveness or quality before marketing [6].

What MK-677 is and what it does

MK-677 (ibutamoren mesylate) is not a peptide and not a SARM. It is an oral small molecule that stimulates growth hormone release by acting on the ghrelin receptor, raising IGF-1 [2]. Merck first synthesized it in 1995 and development stopped in 1999; it has no USP or National Formulary monograph, is not a component of any FDA-approved drug, and is not FDA-approved [2]. A single oral dose is described as long-acting, active for about 24 hours [2].

There is no approved dose. Trials used fixed oral doses of 2 mg to 50 mg per day, most often 25 mg once daily in adults, for up to 2 years [2].

Is the combination studied at all?

Both compounds raise GH and IGF-1, but sermorelin acts on the GHRH receptor and MK-677 on the ghrelin receptor. The trials cited on this page tested each compound on its own; none gave the two together, so how the pair affects IGF-1, glucose or fluid balance has not been measured. What follows is what each has done alone.

What the MK-677 trials found for blood sugar

Higher glucose appeared in several MK-677 trials.

One 12-month comparison in 65 healthy adults aged 60 to 81 found fasting glucose rose about 5 mg/dL on MK-677 25 mg daily (P=0.015), with lower insulin sensitivity [4]. In a six-month trial of 161 older hip-fracture patients assigned to MK-677 or placebo, glucose rose 8.0 mg/dL in the MK-677 group versus a 1.6 mg/dL fall with placebo, and in FDA's review of the trial HbA1c rose 0.7% versus 0.3% [2][12]. In 123 hip-fracture patients treated for 24 weeks, blood glucose and HbA1c rose more on MK-677 than on placebo [3]. In 563 people with mild to moderate Alzheimer's disease treated for 12 months, blood glucose increases occurred in 15.4% versus 4.6% and HbA1c increases in 11.1% versus 1.4% [13]. In 24 obese men treated for 8 weeks, an oral glucose tolerance test showed impaired glucose handling at 2 and 8 weeks [14]. In healthy older adults given 25 mg for 2 to 4 weeks, fasting glucose rose about 25% above baseline (Chapman 1996, as summarized by FDA) [2].

What the MK-677 trials found for fluid and the heart

A multicenter randomized trial in 123 hip-fracture patients, 25 mg daily for 24 weeks, was terminated early for a safety signal of congestive heart failure; per FDA's summary, 4 patients (6.5%) on MK-677 versus 1 (1.7%) on placebo [3][2]. Systolic blood pressure rose 11.9 to 16.4 mmHg on MK-677 against 2.3 to -2.3 mmHg on placebo, serious adverse events occurred in 24% versus 13%, and the authors concluded that MK-0677 has an unfavorable safety profile in this population [3][2].

In a separate 6-month trial in 161 hip-fracture patients, serious adverse events occurred in 24% (20 of 84) versus 18% (14 of 77), thrombosis in 4 versus 0 patients, and edema or fluid overload in 16 versus 10 patients; 12% versus 2.6% stopped treatment for adverse events [12][2].

FDA's stated reason for placing ibutamoren among bulk substances that raise significant safety risks is the potential for congestive heart failure in certain patients, citing the hip-fracture trial terminated early [7][3].

Other effects reported with MK-677

In the 65 healthy older adults, the most frequent side effects were increased appetite, transient mild leg edema and muscle pain; body weight rose 2.7 kg versus 0.8 kg on placebo and fat-free mass rose 1.1 kg versus a 0.5 kg fall, but strength and function did not improve [4]. The same trial found cortisol rose and LDL fell about 5 mg/dL [4].

In the Alzheimer's trial, drug-related adverse events occurred in 35.5% versus 23.9% on placebo, including fatigue, peripheral edema, dizziness, headache and agitation [13]. Liver enzyme rises of 1.5 to 4 times normal, reversible, occurred in some trials, and raised prolactin has been reported [2].

FDA's overall conclusion from the trials lists serious safety concerns including hyperglycemia, liver enzyme elevations, edema and fluid overload, and congestive heart failure in elderly patients recovering from hip fracture; serious events across studies included congestive heart failure, thrombosis, cancer and myocardial infarction [2]. There are no long-term safety data in the older adults MK-677 is marketed to [2]. Three reports reached FDA's adverse event database through October 1, 2023, and published case reports describe liver enzyme elevation, hyperglycemia and abnormal lipids in men also using SARMs, where the role of MK-677 cannot be separated from the other drugs [2][15].

What the sermorelin studies show

A 1-year, open-label, multicenter study in 110 previously untreated prepubertal children with growth hormone deficiency (86 evaluable) gave 30 micrograms per kg subcutaneously at bedtime. Height velocity rose from 4.1 cm/yr at baseline to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months, and 74% were good responders at 6 months [5]. No adverse changes in general biochemical or hormone analyses were noted, fasting glucose did not change, IGF-I was not excessively generated and sermorelin was well tolerated [5].

In 10 healthy older men (mean age 68), 0.5 mg and 1 mg subcutaneously twice daily for 14 days each raised 24-hour growth hormone and IGF-1 at the higher dose to levels not significantly different from 9 younger men; it was a short physiology study, not a trial of clinical benefit [16].

What should be monitored

The measures that changed in the MK-677 trials are the ones with something to track.

• Glucose measures changed in the Nass, Bach, Adunsky and Sevigny studies (fasting glucose, HbA1c or both), and an oral glucose tolerance test showed impaired glucose handling in the Svensson study [4][12][3][13][14].
• In a trial enrolling 292 postmenopausal women across four treatment groups, IGF-1 rose 39% to 45% in the groups receiving MK-677, alone or with alendronate [17]; it rose 72.9% in the Alzheimer's trial [13] and 84% versus 17% in the 6-month hip-fracture trial [12]. FDA notes that older people with high IGF-1 have been observed to have higher risk of disease or death, and that higher IGF-1 appears linked to cancer risk across ages [2].
• Blood pressure rose in the 24-week hip-fracture trial [2].
• Fluid status: edema or fluid overload affected 16 versus 10 patients in one hip-fracture trial, and transient mild leg edema was among the most frequent effects in healthy older adults [12][4].
• Liver enzymes rose 1.5 to 4 times normal in some trials and reversed [2].

There is no FDA label for MK-677 to follow. FDA's review instead notes that, by raising GH and IGF-1, MK-677 may carry the risks listed on approved growth hormone labels: increased risk of neoplasm, glucose intolerance and diabetes, intracranial hypertension, fluid retention, hypoadrenalism, hypothyroidism and pancreatitis, plus slipped capital femoral epiphysis and scoliosis progression in children [2].

Legal status of each compound

MK-677 is not an approved drug and FDA does not treat it as a supplement. In a December 12, 2025 warning letter FDA stated that ibutamoren is excluded from the dietary supplement definition and that products marketed with drug claims are unapproved new drugs [18]. It sits in FDA's category 2 for bulk substances that raise significant safety risks, added December 29, 2022 for outsourcing facilities and September 29, 2023 for state-licensed pharmacies and physicians, and it is still there on the lists updated in 2025 and 2026 [7][19][8]. On October 29, 2024 FDA's Pharmacy Compounding Advisory Committee voted 1 yes, 13 no, 0 abstain against adding ibutamoren mesylate to the pharmacy bulks list [20]. It is not one of the six peptides in HHS's draft enforcement-discretion policy for compounded peptides filed in October 2026 [6][21].

FDA has also found ibutamoren as a hidden ingredient: on September 23, 2025 it warned that a children's product, Agebox iKids Growth Day Formula, contained ibutamoren not listed on the label, and listed risks including increased appetite, water retention, fatigue, muscle pain, changes in glucose metabolism and insulin sensitivity, and a possible increase in congestive heart failure risk in certain individuals [22].

Sermorelin is not on FDA's category 2 page of bulk substances that may raise significant safety risks [7]. It appears on FDA's nominated bulk substance list for outsourcing facilities in category 1, under evaluation, marked as a component of FDA-approved drugs [8], and does not appear in any category on the list for state-licensed pharmacies and physicians [19].

Both are on WADA's Prohibited List: sermorelin and ibutamoren are named in S2.2.4 (growth hormone releasing factors and growth hormone secretagogues), prohibited at all times in and out of competition, on the 2026 list and the 2027 list [9][23].