Sironax has reached roughly 50 percent enrollment in FORGE-LM, a global Phase 2 trial testing SIR4156, an orally active allosteric NAMPT activator, alongside semaglutide in adults with obesity. The compound is designed to raise NAD+ levels and address the lean mass loss that accompanies GLP-1 receptor agonist therapy, with body fat mass and body composition as primary endpoints and lean mass among the secondary measures. Preclinical models showed preferential fat loss, reduced muscle atrophy and improved physical performance, though human safety and efficacy remain unestablished.
Key Points
- Phase 2 trial of NAMPT activator SIR4156 reaches 50% enrollment
- Primary endpoint is body composition; lean mass sits secondary
- Mouse data showed preserved lean mass and reduced muscle atrophy
Longevity Analysis
Lean mass in later life underwrites strength, balance and independence, which makes the muscle cost of rapid pharmacological weight loss a functional question rather than a cosmetic one. Pairing a cellular energy-regulation target with an appetite-modulating hormone pathway reflects a shift from treating weight as a single number to reading body composition as the more informative signal. The design detail worth noting is that lean mass is a secondary endpoint, so the trial will describe composition broadly before it can answer whether muscle is specifically protected — and preclinical performance in rodents does not reliably forecast outcomes in humans.
Original published by Longevity.Technology, by Kyle Umipig.