Objective: Hypoglycaemia poses a significant management challenge in patients with unresectable functional malignant insulinoma. Novel agents such as mammalian target of rapamycin (mTOR) inhibitors and radiolabelled peptides may be effective where there is failure of conventional therapy. Design: We present the cases of two men diagnosed with inoperable malignant insulinoma and hepatic metastases who developed severe symptomatic hypoglycaemia, and review potential therapies for glycaemic support. Method: Despite treatment with diazoxide, frequent oral carbohydrate, prednisolone and somatostatin analogue therapy, both men required hospital admission for treatment with continuous i.v. dextrose. Both were treated with Lutetium-177 octreotate. One man was also treated with everolimus, a mTOR inhibitor. Result: Use of Lutetium-177 octreotate, and in one case everolimus, successfully achieved normoglycaemia, facilitating safe discharge from hospital. Both men also had regression in the size and number of hepatic metastases. Conclusion: Lutetium-177 octreotate and everolimus are options for managing hypoglycaemia due to unresectable malignant insulinoma when refractory to conventional supportive therapies.