Oral ghrelin agonist MK-0677 increased serum IGF-1 by 65% in hemodialysis patients
Background
Patients with end-stage renal disease (ESRD) often suffer from protein-energy wasting (PEW), a condition linked to high morbidity and mortality with few treatment options. While growth hormone (GH) can increase insulin-like growth factor 1 (IGF-1) and improve nutritional status, it requires subcutaneous injection and fails to mimic natural GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), stimulates normal GH secretion and has been shown to increase lean body mass in healthy individuals. This study is the first to evaluate its effects in dialysis patients, a critical step to assess its safety and efficacy before larger clinical trials for PEW can be considered.
Study Design
This was a randomized, double-blind, crossover study designed to assess the effect of MK-0677 versus placebo on serum IGF-1 levels in hemodialysis patients. The primary outcome was the change in IGF-1 concentration. A total of 26 subjects were enrolled, and 22 completed the 3-month crossover protocol. The specific dose of MK-0677 and the frequency of administration are not detailed in the abstract. Each participant served as their own control, receiving both the active drug and the placebo during different phases of the trial.
Results
The study found a significant increase in IGF-1 levels with MK-0677 treatment. After the placebo period, the geometric mean IGF-1 was 1.07-fold greater than baseline (95% CI 0.89-1.27; P = 0.718), showing no significant change. In contrast, following the MK-0677 intervention, the geometric mean IGF-1 was 1.76-fold greater (95% CI 1.48-2.10; P < 0.001). When the data were adjusted for pre-intervention IGF-1 levels, the primary analysis showed a major difference between the groups.
The ratio of geometric means for the pre- versus post-intervention change in IGF-1 (MK-0677 relative to placebo) was 1.65 (95% CI 1.33-2.04; P < 0.001). This demonstrates a 65% greater increase (95% CI 33-104%) in serum IGF-1 in subjects when they received MK-0677 compared to when they received placebo. Importantly, there were no serious adverse effects reported that could be attributed to the MK-0677 treatment during the study period.
Key Findings
- MK-0677 increased geometric mean IGF-1 by 1.76-fold from baseline (P < 0.001).
- Compared to placebo, MK-0677 produced a 65% greater increase in IGF-1 levels (P < 0.001).
- Placebo treatment resulted in no significant change in IGF-1 levels (P = 0.718).
- No serious adverse effects attributable to MK-0677 were observed in this patient population.
Why It Matters
This study establishes that MK-0677 is effective at raising IGF-1 levels in the specific, vulnerable population of hemodialysis patients, a group where anabolic support is critically needed to combat protein-energy wasting. For clinicians and researchers, this provides a strong rationale for moving forward with longer-term trials. The oral route of administration is a significant practical advantage over injectable GH. The key implication is that MK-0677 is a viable candidate for treating muscle and protein loss in ESRD, but its direct impact on lean body mass, physical strength, and survival is not yet proven. Further studies are required to determine if this robust increase in IGF-1 translates into tangible clinical benefits like improved body composition, quality of life, and long-term survival for patients with chronic kidney disease.
TitrateLab articles covering MK-677
Written by TitrateLab, separately from the study summarized above.
