MK-677: A Real Trial in Eight People, and a Liver Report

MK‑677 is marketed to people losing weight who are worried about losing muscle, and there is a real trial behind that claim. In a double-blind, randomized, placebo-controlled crossover study, calorically restricted volunteers on MK‑677 moved from negative to positive nitrogen balance while placebo stayed negative — +0.31 against −1.48 g/day, P < 0.01.^[1] The trial had eight participants, ran the drug for seven days, and measured a laboratory proxy rather than muscle. A 2025 case report describes liver injury in a healthy man after two months of taking it.^[2]

The trial, and what it actually measured

Eight healthy volunteers aged 24 to 39 were calorically restricted to 18 kcal/kg/day for two 14-day periods. In the last seven days of each period they received either oral MK‑677 25 mg once daily or placebo, with a washout of 14 to 21 days between. During the first week — diet alone, no drug — nitrogen losses were essentially identical between the groups, which is a good sign that the design was working.^[1]

That is a clean result and it should be said plainly: on this endpoint, in this design, the drug did what it was supposed to. Crossing from nitrogen loss into nitrogen retention during a calorie deficit is not nothing.

The liver report

In 2025 clinicians published the case of an otherwise healthy man in his early thirties who developed transaminitis — raised liver enzymes — after taking MK‑677 for two months. Liver function tests returned to normal after he stopped. The authors note that reports of hepatotoxicity with this compound are scarce, while acknowledging its growing popularity as a performance supplement.^[2]

One case is one case. It cannot tell you the risk, and this article is not going to imply a rate that nobody has measured. What it does establish is that liver injury is on the list of things that have happened, in a healthy young person, at a dose and duration that is unremarkable for how this compound is used.

The commoner reported effects — edema, increased appetite, muscle pain — are worth knowing too, and the appetite one is worth a moment’s thought if you are taking it alongside a drug whose entire purpose is to reduce appetite.

What it is, and what that means for what you buy

• MK-677 is a growth hormone secretagogue — an orally active non-peptide that prompts the body to release its own growth hormone. It is not itself a peptide, despite usually being sold alongside them.
• It is not an approved medicine. It is sold as a research chemical, outside the identity, purity and dose standards that apply to prescription drugs.
• The muscle-preservation case rests on a 1998 crossover trial in eight people measuring a proxy endpoint.
• ⚠ Raising growth hormone and IGF-1 has implications that go beyond muscle. Anyone with a history of cancer, or with diabetes, has particular reason to take that to a clinician rather than a forum.

If muscle loss during weight loss is your actual concern, the interventions with real randomized support are covered in what the body-composition studies measured, protein targets and the lab panel and bone density and exercise. Resistance training is the one that keeps appearing.