Systematic review of multimodal management strategies for Insulinoma-Induced hypoglycaemia: current evidence and future directions.

Purpose The most common functional neuroendocrine neoplasms are insulinomas, representing the leading cause of endogenous hyperinsulinemic hypoglycaemia. The management of insulinoma remains a challenge for clinicians, especially when surgery is neither feasible nor curative. This review aims to evaluate hypoglycaemia-relief drugs for insulinoma, focusing on their effectiveness in glycaemic control, potential impact on tumour burden, and safety. Methods A comprehensive and systematic review of the literature was performed including traditional hypoglycaemia-relief drugs (diazoxide, glucocorticoids and somatostatin analogues) and newer therapies such as everolimus, sunitinib, Peptide Receptor Radionuclide Therapy (PRRT), radiological debulking approaches and chemotherapy regimens. The drug’s half-life, dosing regimen, route of administration, and safety profile were analysed, along with efficacy in glycaemic control and potential reduction in disease burden. Results Benign insulinomas are usually effectively managed with surgical resection, which typically results in symptom resolution. However, advanced and aggressive insulinomas often require a multimodal approach based on systemic drugs and/or minimally invasive radiological techniques. Symptom-relief medications (diazoxide and glucocorticoids) can control hypoglycaemia in selected patients, while other agents (somatostatin analogues, everolimus, PRRT, sunitinib, capecitabine/temozolomide chemotherapy, and debulking techniques) can variably improve both glycaemic control and tumour burden. Conclusion Achieving euglycemia in insulinoma patients, particularly those with metastatic disease, is challenging and requires a comprehensive treatment strategy. This review highlights the need for individualised therapy combining hypoglycaemia-relief drugs, surgical options, and advanced treatments to optimise patient outcomes and improve the quality of life. Further studies are essential to determine optimal sequencing and combination therapies to manage both hypoglycaemia and tumour progression effectively.