Development of pharmacological interventions for the treatment of sarcopenia.

Sarcopenia is a multifactorial age-related muscle disorder of which its underlying pathophysiological mechanisms remain incompletely understood. To date, treatment strategies of sarcopenia have been largely confined to lifestyle interventions, underscoring an urgent need for pharmacological options that directly target the biological drivers of muscle deterioration. Despite increasing interest in drug development for sarcopenia, no specific pharmacological agent has yet received regulatory approval. This review provides a comprehensive synthesis of recent advances in investigational pharmacotherapeutic options for sarcopenia, with a focus on their mechanistic pathways and evidence from clinical trials. Key emerging classes include selective androgen receptor modulators (SARMs), myostatin antibodies, monoclonal antibodies targeting activin type 2 receptors, ghrelin receptor agonists, and growth differentiation factor-15 (GDF-15) monoclonal antibodies. In parallel, existing medications including testosterone, antidiabetic agents, classical renin-angiotensin system (RAS) inhibitors and anti-inflammatory drugs, have shown ancillary benefits in older populations but lack robust, indication-specific data. A critical contradiction persists: while several candidates increase muscle mass, few consistently improve muscle strength or physical function, reflecting a disconnect between surrogate endpoints and clinically meaningful outcomes. Moreover, some trials have been conducted in heterogeneous populations without clearly defined sarcopenia, limiting interpretability. As mechanistic insights evolve and regulatory frameworks advance, the field requires not only more targeted therapies but also clearer definitions of efficacy and patient classification.