MK-677 vs Ipamorelin: differences, evidence and safety

Verdict: MK-677 (ibutamoren) is an oral, non-peptide ghrelin-receptor agonist with several human randomized trials; ipamorelin is an injected five-amino-acid peptide with one published human efficacy trial, which was negative. Neither is FDA approved, both sit in FDA compounding Category 2, and WADA prohibits both.

MK-677 vs ipamorelin is a comparison between two drugs that switch on the same receptor, the growth hormone secretagogue receptor (GHSR, the ghrelin receptor), and push the pituitary to release growth hormone (GH). The strongest evidence for MK-677 is a two-year human RCT in 65 healthy older adults that raised GH, IGF-1 and fat-free mass but also raised fasting glucose and lowered insulin sensitivity. The strongest evidence for ipamorelin is a phase 2 RCT after bowel surgery (n=117) that found no difference from placebo. No study has compared the two directly, and neither has shown better strength or function in people.

Item	MK-677 (ibutamoren)	Ipamorelin
US FDA status	Not approved for any use	Not approved for any use
Compounding (503A/503B)	Category 2, 503A and 503B (heart failure signal)	Category 2, 503B; 503A nomination withdrawn
WADA 2026	Prohibited, S2.2.4, at all times	Prohibited, S2.2.4, at all times
Strongest evidence	Human RCTs (n=24 to 563)	One human RCT (n=117), null result
Human trials	Several; e.g. NCT00474279, NCT00074529, NCT00128115	Two phase 2: NCT00672074, NCT01280344
Main risk signal	Glucose rise, edema, heart failure signal	FDA cites serious events, including death, with IV use
Last checked	2026-10-01	2026-10-01

MK-677 vs ipamorelin at a glance

Feature	MK-677	Ipamorelin
What it is	Small molecule, not a peptide	Pentapeptide: Aib-His-D-2-Nal-D-Phe-Lys-NH2
Class	GH secretagogue, ghrelin mimetic	GH-releasing peptide (GHRP), ghrelin mimetic
Receptor	GHSR (cryo-EM structure solved)	GHRP-type receptor (GHSR)
Developer	Merck (MK-0677); now Lumos (LUM-201)	Novo Nordisk; later Helsinn
Main research focus	Ageing, frailty, obesity, bone, Alzheimer disease, child GH deficiency	GH release, postoperative ileus (slow gut after surgery)
Human efficacy RCTs	Many (8 weeks to 2 years)	One published (n=117)
Routes studied	Oral, once daily	Intravenous in humans; injected in animals
Approval	None (FDA)	None (FDA)
WADA	S2.2.4, prohibited	S2.2.4, prohibited
Timelines in studies	IGF-1 up by 2 weeks; lean mass up by 8 weeks	GH peak about 40 min after an IV infusion
Main safety concerns	Blood glucose, insulin resistance, edema, heart failure signal, appetite	Almost no human safety data; FDA immunogenicity and impurity concerns

What is MK-677?

MK-677, also called ibutamoren mesylate or MK-0677, is an orally active compound that Merck chemists described in 1995, designed to copy the action of ghrelin, the “hunger hormone” made in the stomach. It is not a peptide, even though it is often sold and discussed alongside peptides. A 2021 cryo-electron microscopy study showed exactly how it binds the human ghrelin receptor [Lab]. Merck tested it in older adults, hip-fracture patients, obese men, osteoporosis and Alzheimer disease. It was never approved. Lumos Pharma now develops it as LUM-201 for children with growth hormone deficiency [Human trial, ongoing].

What is ipamorelin?

Ipamorelin is a synthetic pentapeptide (five amino acids) developed at Novo Nordisk and described in 1998 as “the first selective growth hormone secretagogue”. In rats and pigs it released GH about as strongly as GHRP-6; in pigs, unlike GHRP-6 and GHRP-2, it did not raise ACTH or cortisol [Animal]. Because it is a peptide, it breaks down in the gut and has been studied only as an injection or infusion. It is often sold paired with CJC-1295, a combination covered in our evidence review of the Joe Rogan peptides. It is not an FDA-approved drug.

How they work differently

Both drugs activate the same receptor, so the differences lie in chemistry, route and how long the signal lasts.

• MK-677: taken by mouth once a day, it produced a sustained rise. In 32 older adults, it raised mean 24-hour GH by 97% and brought IGF-1 into the young-adult range within two to four weeks, by making existing GH pulses larger rather than adding pulses [Human RCT, n=32].
• Ipamorelin: in healthy men given a 15-minute intravenous infusion, it produced a single GH burst peaking at about 0.67 hours that fell back to negligible levels, with a terminal half-life of about two hours [Human pharmacology study, eight men per infusion level].
• MK-677: the ghrelin-like action also drives hunger. In the two-year trial, increased appetite was the most frequent side effect and faded over a few months [Human RCT, n=65].
• Ipamorelin: it also acts on the gut and appetite. In mice it increased food intake and body fat through a GH-independent route [Animal], and in rats after abdominal surgery it shortened the time to the first bowel movement [Animal].
• Hormone selectivity: ipamorelin’s lack of cortisol release is an animal finding. For MK-677, human data are mixed: cortisol rose only briefly in obese men [Human RCT, n=24] but stayed higher in the older-adult trial [Human RCT, n=65].

Evidence head-to-head

The table scores the best available study for each outcome. No trial has put the two drugs side by side, so every row compares separate studies in different people.

Outcome	MK-677 best evidence	Ipamorelin best evidence
Raises GH / IGF-1	Human RCT, n=65, 2 years: GH and IGF-1 to young-adult levels (Nass 2008)	Human pharmacology, IV: one GH burst per infusion (Gobburu 1999)
Lean (fat-free) mass	Human RCT, n=65: +1.1 kg vs −0.5 kg on placebo at 12 months (Nass 2008)	No human data; animal weight gain only (Johansen 1999)
Body fat	Human RCT: no change in visceral or total fat; limb fat rose (Nass 2008)	Animal: body fat rose in mice (Lall 2001)
Strength and function	Human RCTs: no gain in strength in older adults; most function tests unchanged after hip fracture (Adunsky 2011)	Animal: muscle strength kept in steroid-treated rats (Andersen 2001)
Bone	Human RCT, n=292: MK-677 added to alendronate raised femoral-neck BMD by 4.2% vs 2.5% with alendronate alone; MK-677 alone showed no added gain at spine or hip (Murphy 2001)	Animal: larger bones, unchanged mineral density in rats (Svensson 2000)
Sleep	Small human crossover, n=14: more deep and REM sleep (Copinschi 1997)	No human or animal sleep data found
Gut recovery after surgery	Not studied	Human RCT, n=117: no difference from placebo (Beck 2014)
Kidney failure wasting	Human crossover RCT, 22 completers: IGF-1 up 65% vs placebo (Campbell 2018)	Not studied
Alzheimer disease	Human RCT, n=563: no effect on progression (Sevigny 2008)	Not studied

Read across the rows, MK-677 has far more human data, and that data shows both what it does (raises GH, IGF-1 and lean mass) and what it has not done (improve strength, function or Alzheimer symptoms). Ipamorelin’s human record is two pharmacology and surgery studies; almost everything claimed for it online rests on rodent work. More data does not mean safer: the larger record is also why MK-677’s risks are better known.

Which fits which goal?

These are statements about where the evidence sits, not advice to use either drug.

• Raising GH and IGF-1 over months: MK-677 has more evidence. The two-year older-adult trial kept both in the young-adult range [Human RCT, n=65]. Ipamorelin has only single-infusion human data.
• Lean mass: MK-677 has more evidence. In obese men, fat-free mass rose over eight weeks while total and visceral fat did not change [Human RCT, n=24]. The extra lean mass did not translate into strength in older adults.
• Fat loss: neither has human evidence of fat loss. MK-677 trials found no fall in fat mass, and ipamorelin increased fat in mice.
• Sleep: only MK-677 has a sleep study, a 14-person crossover [Human, small].
• Gut motility after surgery: only ipamorelin was tested, and the phase 2 trial missed its endpoint (median time to a tolerated meal 25.3 vs 32.6 hours, p=0.15).

A clinician who knows a person’s glucose, heart and hormone history is the person to decide whether any GH-axis treatment is appropriate.

Can they be combined?

Online forums and clinic pages sometimes describe taking MK-677 and ipamorelin together, or ipamorelin with CJC-1295 alongside MK-677. Because both drugs act on the same receptor, the rationale offered is usually a larger GH signal. No controlled human study has tested the combination, and no published trial has measured glucose, cortisol, edema or heart effects when the two are used together. A 2026 clinical review of GH-axis peptides lists dysglycemia, fluid retention, prolactin and cortisol changes and joint pain among the adverse effects clinicians see in people using such products, and notes the uncertainty about what unregulated products contain.

Safety and regulatory status

MK-677 risks, from human studies. In the two-year trial, fasting glucose rose by an average 5 mg/dL and insulin sensitivity fell; edema in the legs and muscle pain were common, and body weight rose 2.7 kg vs 0.8 kg on placebo [Human RCT, n=65]. In older adults, fasting glucose rose from 5.4 to 6.8 mmol/L at four weeks [Human RCT, n=32], and in obese men an oral glucose tolerance test worsened [Human RCT, n=24]. The hip-fracture study was terminated early for congestive heart failure in a limited number of patients [Human RCT, n=123]. Case reports describe reversible liver injury in a man in his 30s and gynecomastia and low testosterone from supplements containing MK-677 plus other banned drugs and undeclared hormones [Human case reports, n=1 each].

Ipamorelin risks. Human safety data are thin. In the surgery trial, adverse events were 87.5% with ipamorelin vs 94.8% with placebo, in patients recovering from bowel resection [Human RCT, n=114 analysed]. The larger follow-up trial of 320 patients, NCT01280344, finished in 2014 with no results posted on the registry. There are no long-term human studies of repeated injections.

United States (FDA). Neither drug is approved. On the FDA’s Category 2 list of bulk substances that carry possible safety risks (page current as of 2026-04-22), ibutamoren mesylate is listed for both 503A pharmacies (since 2023-09-29) and 503B outsourcing facilities (since 2022-12-29), citing the heart failure signal, cortisol effects and glucose rise. Ipamorelin acetate is listed for 503B (since 2023-09-29); its 503A nomination sits in the page’s “withdrawn by nominators” table. The FDA cites immunogenicity risk from aggregation and impurities, notes unnatural amino acids and states that a published study “identified serious adverse events including death” with intravenous ipamorelin for gastric motility. Removal of a 503A nomination does not approve a substance.

Sport (WADA). The 2026 Prohibited List names both “ibutamoren (MK-677)” and “ipamorelin” as growth hormone secretagogues under S2.2.4, prohibited at all times, in and out of competition. Supplements can also carry MK-677 without the athlete knowing: in the European and international lab survey, 24% of seized products were presented as dietary supplements.

How long do effects take in studies?

• MK-677, hormones: IGF-1 in older adults rose from 141 to 219 µg/L at two weeks and 265 µg/L at four weeks in the 1996 trial [Human RCT, n=32].
• MK-677, body composition: fat-free mass was up at eight weeks in obese men, and basal metabolic rate was higher at two weeks but not at eight [Human RCT, n=24]. In older adults the lean-mass gain was measured at 12 months and held at 24 [Human RCT, n=65].
• MK-677, sleep: changes in deep and REM sleep were recorded after 7 to 14 days of bedtime use in the crossover study [Human, n=14].
• Ipamorelin: the GH peak came about 40 minutes after an intravenous infusion and faded within hours in healthy men [Human pharmacology]. In rats, faster bone growth was measured over 15 days [Animal]. No human study reports a timeline for body composition.