Paltusotine: The first selective nonpeptide agonist of somatostatin receptor 2 (SSTR2) for the treatment of acromegaly.

Abstract

Acromegaly is an endocrine disorder characterized by abnormal enlargement of the extremities and internal organs resulting from excessive secretion of growth hormone (GH) by the pituitary gland, which in turn leads to elevated levels of insulin-like growth factor 1 (IGF-1). Approximately 45% of patients remain biochemically uncontrolled after surgery and require long-term treatment with injectable somatostatin analogs such as octreotide or lanreotide. These polypeptide drugs generally require monthly administration to maintain disease control; however, many patients experience recurrence of symptoms towards the end of the dosing interval. Moreover, injection-site pain and local reactions are common, significantly impacting patients' quality of life. On September 25, 2025, the U.S. Food and Drug Administration (FDA) approved paltusotine, the first once-daily oral, nonpeptide somatostatin receptor 2 (SSTR2) agonist for the treatment of acromegaly. By enabling oral rather than injectable therapy, paltusotine reduces the treatment burden and enhances patient adherence. With its rapid onset and durable biochemical control, this novel agent has the potential to reshape the current paradigm of acromegaly pharmacotherapy and offer patients a more convenient and effective treatment option. Nevertheless, its long-term safety and efficacy warrant further evaluation in real-world clinical settings.