Pasireotide-induced hyperglycemia in Cushing's disease and Acromegaly managed by incretin-based therapy or insulin

Patients with Cushing's disease or Acromegaly often require somatostatin analogs like pasireotide for tumor control. A significant side effect of pasireotide, particularly its long-acting release (LAR) formulation, is the induction of hyperglycemia and diabetes mellitus. This occurs due to pasireotide's agonism at somatostatin receptor subtype 5 (SSTR5), which inhibits insulin secretion from pancreatic beta cells. Current standard-of-care often starts with metformin, but many patients fail to achieve adequate glycemic control, necessitating further therapeutic strategies.

This Phase IV, multi-center, randomized, open-label study investigated hyperglycemia management in adult patients with Cushing's disease or Acromegaly receiving pasireotide s.c. or pasireotide LAR. Participants who developed diabetes on pasireotide and failed to achieve glycemic targets with metformin within 16 weeks were randomized 1:1 to receive either incretin-based therapy or insulin for approximately 16 weeks. Eligible patients were either new to pasireotide or already on it, provided they met protocol criteria for hyperglycemia unmanageable by metformin. An optional Extension Phase allowed continued treatment for patients benefiting clinically.