Impact of Metformin on Systemic Metabolism and Survival of Patients With Advanced Pancreatic Neuroendocrine Tumors

Vernieri, Claudio; Pusceddu, Sara; Braud, Filippo de

doi:10.3389/fonc.2019.00902

Cited by 9 publications

(13 citation statements)

References 24 publications

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“…Therefore, future studies should further be refined by NET type as well as Ki67 and tumor grade. In addition, data on management of DM were recorded for oral versus insulin therapy, but data for the specific use of metformin was not collected, which would be important to evaluate as studies have recently shown metformin to be a potential contributor to survival in patients with pancreatic NETs [ 18 , 33 , 34 ] through a mechanism related to dose-dependent suppression of cell proliferation [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Implications of Neuroendocrine Tumor and Diabetes Mellitus on Patient Outcomes and Care: a Matched case–control Study

et al. 2021

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Aim: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control. Patients & methods: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005–2017), and survival compared (Kaplan–Meier and Cox proportional hazards). Mixed models compared hemoglobin A1c (HbA1c) and glucose during the year after cancer diagnosis. Results: Three-year overall survival was 72% (95% CI: 60–86%) for DM patients versus 80% (95% CI: 70–92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56–3.16; p = 0.51); mean DM HbA1c, 7.3%. Conclusion: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control.

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Section: Discussionmentioning

confidence: 99%

Implications of Neuroendocrine Tumor and Diabetes Mellitus on Patient Outcomes and Care: a Matched case–control Study

et al. 2021

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“…The potential antitumor activity of metformin is determined by systemic actions and direct actions on cells [ 3 , 7 , 184 , 185 , 186 , 187 , 188 ].…”

Section: Cell Signaling and The Anticancer Activity Of Metforminmentioning

confidence: 99%

“…At a systemic level, metformin reduces insulin resistance and improves plasma glucose control, thus decreasing hyperinsulinemia, insulin receptor activation in neoplastic cells and pre-neoplastic cells, and glucose concentration in the tumor microenvironment. Moreover, metformin can decrease the expression of proinflammatory cytokines and circulating proinflammatory cytokine levels [ 7 , 187 , 190 ].…”

Section: Cell Signaling and The Anticancer Activity Of Metforminmentioning

confidence: 99%

“…The analysis of the progression free survival (PFS) in diabetic patients treated with metformin compared to diabetic patients not treated with metformin and non-diabetic patients, suggested a direct or indirect antitumor activity of metformin. Moreover, metformin administration improved the efficacy of the pharmacological antitumor therapies based on somatostatin analogs or everolimus [ 17 , 187 , 243 , 244 , 245 ].…”

Section: Metformin Actions On Pituitary Tumor Cells and Gastroenteropancreatic Neuroendocrine Tumor Cellsmentioning

confidence: 99%

“…Metformin inhibited the cellular proliferation of neuroendocrine tumor cells of different origins and reduced cell viability in two pNET cell lines (BON-1 and QPG-1). Actually, the effective metformin concentrations in cell growth media exceeded the plasma metformin levels reached in patients treated with safe dosages, just as in studies with pituitary tumor cell cultures [ 13 , 187 , 246 , 247 , 248 , 249 ].…”

Section: Metformin Actions On Pituitary Tumor Cells and Gastroenteropancreatic Neuroendocrine Tumor Cellsmentioning

confidence: 99%

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Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

Tulipano

2021

IJMS

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Metformin is considered the first-choice drug for type 2 diabetes treatment. Actually, pleiotropic effects of metformin have been recognized, and there is evidence that this drug may have a favorable impact on health beyond its glucose-lowering activity. In summary, despite its long history, metformin is still an attractive research opportunity in the field of endocrine and metabolic diseases, age-related diseases, and cancer. To this end, its mode of action in distinct cell types is still in dispute. The aim of this work was to review the current knowledge and recent findings on the molecular mechanisms underlying the pharmacological effects of metformin in the field of metabolic and endocrine pathologies, including some endocrine tumors. Metformin is believed to act through multiple pathways that can be interconnected or work independently. Moreover, metformin effects on target tissues may be either direct or indirect, which means secondary to the actions on other tissues and consequent alterations at systemic level. Finally, as to the direct actions of metformin at cellular level, the intracellular milieu cooperates to cause differential responses to the drug between distinct cell types, despite the primary molecular targets may be the same within cells. Cellular bioenergetics can be regarded as the primary target of metformin action. Metformin can perturb the cytosolic and mitochondrial NAD/NADH ratio and the ATP/AMP ratio within cells, thus affecting enzymatic activities and metabolic and signaling pathways which depend on redox- and energy balance. In this context, the possible link between pyruvate metabolism and metformin actions is extensively discussed.

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Prognostic value of preoperative diabetes mellitus in patients with non-functional pancreatic neuroendocrine neoplasms

Tan

Wang

Chen

et al. 2022

The American Journal of Surgery

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Impact of Metformin on Systemic Metabolism and Survival of Patients With Advanced Pancreatic Neuroendocrine Tumors

Cited by 9 publications

References 24 publications

Implications of Neuroendocrine Tumor and Diabetes Mellitus on Patient Outcomes and Care: a Matched case–control Study

Implications of Neuroendocrine Tumor and Diabetes Mellitus on Patient Outcomes and Care: a Matched case–control Study

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

Prognostic value of preoperative diabetes mellitus in patients with non-functional pancreatic neuroendocrine neoplasms

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