Background
HIV-associated adipose redistribution syndrome (HARS) — lipodystrophy — involves visceral fat accumulation and peripheral fat wasting, associated with metabolic complications and reduced quality of life. GH axis dysregulation contributes to this phenotype.
This trial evaluated MK-677 (ibutamoren) alongside tesamorelin (a GHRH analog approved for HIV lipodystrophy) for body composition improvement in this population — one of the few controlled trials assessing MK-677 at clinical endpoints beyond GH levels.
Methods
Phase 3, randomized, double-blind, placebo-controlled trial. HIV-positive adults on stable antiretroviral therapy with visceral adiposity. Arms: MK-677 25 mg daily, tesamorelin 2 mg daily, or placebo for 12 months. Primary endpoints: trunk fat change (DXA), visceral adipose tissue (CT).
Key Findings
| Outcome | MK-677 25 mg | Placebo | p-value |
|---|---|---|---|
| Lean body mass change | +1.8 kg | −0.2 kg | 0.002 |
| Trunk fat change | −0.6 kg | +0.3 kg | 0.04 |
| IGF-1 | +79% | No change | <0.001 |
| Fasting glucose | Mild increase | No change | — |
| Bone mineral density | No change | — | — |
Clinical Significance
This is one of the few rigorous long-term trials demonstrating body composition improvements with an oral GH secretagogue. The lean mass gains (+1.8 kg over 12 months) and modest visceral fat reduction are consistent with the expected effects of GH axis stimulation.
The mild hyperglycemia seen with MK-677 reinforces the importance of glucose monitoring during secretagogue therapy, particularly in metabolically compromised populations.
Limitations
- Specific disease population (HIV-HARS) — effects may differ in healthy adults
- Primary comparator was tesamorelin (a GHRH analog), not placebo only
- Glucose elevation warrants caution in pre-diabetic patients
- 12-month duration; long-term effects on outcomes not established