Unexpected Insulinoma in Type 2 Diabetes During Long-term Dulaglutide Therapy: A Case Report and Literature Review
Abstract
Abstract The coexistence of insulinoma and diabetes mellitus is rare and poses significant diagnostic challenges, with evidence largely limited to isolated case reports, predominantly involving patients with type 2 diabetes treated with insulin, sulfonylureas, or metformin. To the best of our knowledge, this is the first reported case of insulinoma diagnosed in a patient with long-standing type 2 diabetes receiving long-term GLP-1RA therapy. A 76-year-old man treated with dulaglutide and empagliflozin developed recurrent fasting hypoglycemia over several months, characterized by autonomic and neuroglycopenic symptoms fulfilling Whipple’s triad. Discontinuation of antidiabetic therapy did not resolve hypoglycemia, which was objectively documented by continuous glucose monitoring (CGM). A prolonged fasting test confirmed endogenous hyperinsulinism, and imaging revealed a hypervascular pancreatic lesion. The patient underwent subtotal splenopancreatectomy, and histology demonstrated a well-differentiated insulin-secreting neuroendocrine tumor. In the era of modern glucose-lowering therapies, this case highlights the importance of considering endogenous hyperinsulinism in patients with type 2 diabetes who present with persistent hypoglycemia despite withdrawal of antidiabetic agents and supports the use of CGM as a valuable additional tool in the diagnostic workup. While current clinical evidence does not support a causal association between GLP-1RA and neuroendocrine tumors,…
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