Diabetes mellitus (DM) and pancreatic neuroendocrine tumors (pNETs) are two entities closely linked together. DM has been described as a risk factor for the development of pNETs and for the aggressiveness of the disease. On the other hand, DM due to pNETs is frequently undiagnosed or misclassified as type 2 DM when it is due to type 3 DM. In addition, metformin, a commonly prescribed drug for type 2 DM, has an antiproliferative property and is gaining increasing attention as an antitumor agent. This review article presents the findings published in the last few years on pNETs and DMs. Emphasis will be placed on DM as a risk factor, pNET as a risk factor for the development of type 3 DM, the management of type 3 DM on pNET, and DM as a prognostic factor in patients with pNET, as well as the future clinical implications of DM in these patients. The coexistence of DM and pNET is extensively presented. It is important to perform future clinical trials, which are necessary to establish the role of metformin on pNET disease. Increasing awareness among professionals managing pNET on the importance of a correct DM diagnosis and management of the disease must be a priority due to the implications on mortality and comorbidities it may have in these patients.

Background: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. Objective: This review aims to provide a comprehensive overview of the physiopathology of malnutrition in functioning GEP-NENs and to highlight nutritional and supportive care strategies, including how medical, surgical, and locoregional treatments can indirectly improve nutritional outcomes. Methods: We analyzed the current literature and clinical guidelines to identify key mechanisms of malnutrition across different functioning syndromes and their clinical manifestations. Nutritional recommendations and the impact of treatment modalities on nutritional status were summarized. Results: The pathophysiology of malnutrition in functioning NENs is multifactorial and syndrome-specific. Hormonal hypersecretion may cause diarrhea, electrolyte imbalances, catabolic states, steatorrhea, or hypoglycemia, among other effects. These lead to nutrient loss, malabsorption, or altered intake. Tailored dietary interventions, micronutrient supplementation (e.g., niacin, calcium, vitamin B12), and symptom-guided nutritional support are essential. Somatostatin analogs, PRRT, and cytoreductive approaches often contribute to symptom control, thereby enhancing nutritional status and patient quality of life. Conclusions: Malnutrition in functioning GEP-NENs is a significant clinical issue that requires early recognition and a multidisciplinary, individualized management plan. Integrating nutrition into the comprehensive care of these patients is essential to improve outcomes and quality of life.