MK-677 (Ibutamoren)

What MK-677 is

MK-677, also called ibutamoren, activates the ghrelin receptor, also known as the growth hormone secretagogue receptor, in the pituitary gland and thereby triggers releases of growth hormone and, as a consequence, of IGF-1. Unlike the peptides of this class, the substance works orally.

That this mechanism works in humans is undisputed and confirmed in several randomized trials. The real question is whether the hormone rise leads to a benefit you notice: more strength, better function, less fat. It is exactly at this point that the data break off.

Mass is not function

IGF-1 and lean mass are surrogate markers, that is, measures that stand in for a hoped-for benefit. Whether actual strength or everyday function results from them must be tested separately, and it has been tested.

A review of sarcopenia drugs summarizes the state of knowledge for the entire substance class: several candidates increase muscle mass, only a few consistently improve muscle strength or physical function. The authors explicitly speak of a discrepancy between surrogate endpoints and clinically meaningful outcomes. No agent in this class is approved.

What the studies show

Two years, 65 older adults: mass yes, function no

The largest and longest trial was double-blind, randomized and placebo-controlled in a modified crossover design: 65 healthy adults between 60 and 81 years received 25 mg MK-677 orally daily for two years. Primary endpoints at one year were lean mass and abdominal visceral fat. Lean mass was met: minus 0.5 kg (95% CI -1.1 to 0.2) on placebo versus plus 1.1 kg (0.7 to 1.5) on MK-677, p<0.001. Visceral fat was missed, as was total fat mass. Body weight rose by 0.8 kg (-0.3 to 1.8) versus 2.7 kg (2.0 to 3.5), p=0.003, with the gain in limb fat being greater on MK-677 (1.1 kg versus 0.24 kg, p=0.001).

The sentence that matters

Isokinetic strength, physical function and quality of life were measured in the same trial. None of these measures improved. The authors state verbatim that the increased lean mass did not lead to any changes in strength or function. As a limitation, they themselves cite insufficient statistical power for the functional endpoints. What is demonstrated is therefore a change in body composition, not a noticeable benefit.

Hip fracture patients: stopped early

A randomized, double-blind, multicenter phase IIb trial gave 123 older hip fracture patients (62 versus 61) 25 mg daily over 24 weeks. The IGF-1 endpoint was met, plus 51.4 ng/ml (95% CI 34.42 to 68.44), p<0.001. Function was missed: stair-climbing power was plus 12.5 watts (95% CI -10.95 to 35.88, p=0.292); the confidence interval includes zero. The only positive measure was gait speed, with a score difference of 0.7 (0.17 to 1.28, p=0.011). The trial was stopped early because of a safety signal for heart failure. The authors’ conclusion is that MK-677 had an unfavorable safety profile in this patient group.

Dialysis patients: a pure lab-value endpoint

A randomized, double-blind crossover trial over three months in hemodialysis patients enrolled 26 people; 22 completed it. The primary endpoint IGF-1 was met, with a 65% greater rise versus placebo (95% CI 33 to 104%; ratio of geometric means 1.65, 1.33 to 2.04, p<0.001). The authors conclude by stating that studies are needed to test whether MK-677 improves strength, quality of life and survival. A clinical or functional benefit was not shown.

What the studies do not show

• More strength. The two-year trial explicitly stated that the increased lean mass did not lead to any change in strength or function.
• Better physical function. In none of the randomized trials evaluated was a functional improvement shown as a met primary endpoint.
• Fat loss. Visceral fat was a primary endpoint and was missed; total fat mass did not change either. The gain in limb fat was actually greater on MK-677.
• An anti-aging benefit. What is demonstrated is body composition and lab values. These lab values go hand in hand with rising fasting glucose, falling insulin sensitivity and rising cortisol.

Status, approval and legal

MK-677 is not an approved medicine but a research substance. Even for the indication sarcopenia, no agent in this class is approved. In competitive sport the substance is banned.

It is traded as a research product, that is, without pharmaceutical quality control. One documented case report concerned preparations that contained, in addition to MK-677, other active substances as well as undeclared testosterone, estradiol and growth hormone.

Safety

In the two-year trial, fasting glucose rose by 0.3 mmol/l, that is, 5 mg/dl (p=0.015), insulin sensitivity fell, and cortisol rose by 47 nmol/l (28 to 71, p=0.020). These are not marginal findings but the flip side of the hormone effect: metabolism measurably worsens while lean mass increases.

The phase IIb trial in hip fracture patients was stopped early because of a safety signal for heart failure; the authors attested an unfavorable safety profile in this group. In addition there are case reports: liver injury after two months of MK-677, with transaminases that normalized after stopping, as well as gynecomastia and hypogonadotropic hypogonadism with mixed preparations.

Sources

• Nass et al. 2008, Annals of Internal Medicine – double-blind, placebo-controlled, 2 years, 65 participants (PMID 18981485)
• Adunsky et al. 2011, Archives of Gerontology and Geriatrics – phase IIb, n=123, stopped early (PMID 21067829)
• Campbell et al. 2018, Nephrology Dialysis Transplantation – randomized crossover, hemodialysis, n=22 (PMID 28340044)
• Yang et al. 2026, Annals of Translational Medicine – review of sarcopenia drugs (PMID 42164047)
• BMJ Case Reports 2025 – liver injury after two months of MK-677 (PMID 40675653)
• JCEM Case Reports 2024 – gynecomastia and hypogonadotropic hypogonadism with mixed preparations (PMID 39145153)