Amir Sonnenblick, Dominique Agbor-Tarh, Ian Bradbury, Serena Di Cosimo, Hatem A Azim, Debora Fumagalli, Severine Sarp, Antonio C Wolff, Michael Andersson, Judith Kroep, Tanja Cufer, Sergio D Simon, Pamela Salman, Masakazu Toi, Lyndsay Harris, Julie Gralow, Maccon Keane, Alvaro Moreno-Aspitia, Martine Piccart-Gebhart, Evandro de Azambuja
Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination...
May 1, 2017: Journal of Clinical Oncology
Choong-kun Lee, Minkyu Jung, Inkyung Jung, Su Jin Heo, Yong Hyu Jeong, Ji Yeong An, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyo Song Kim, Sun Young Rha, Hyun Cheol Chung
OBJECTIVE: The aim of this study was to evaluate the association between metformin and survival of gastric cancer (GC) patients. BACKGROUND: Metformin has recently received attention as a potential anticancer treatment. However, no study has shown the survival benefit of metformin for GC patients. METHODS: A total of 1974 GC patients who underwent curative gastrectomy were compared for survival according to groups; 132 diabetic patients treated with metformin, 194 diabetic patients without metformin, and 1648 non-diabetic patients...
January 2016: Annals of Surgery
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer...
September 2017: Molecular Cancer Therapeutics
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the proapoptotic machineries in various p53-defective cancer cells...
September 2017: Molecular Cancer Therapeutics
Qiao-Li Wang, Giola Santoni, Eivind Ness-Jensen, Jesper Lagergren, Shao-Hua Xie
OBJECTIVES: Esophageal cancer is a highly fatal malignant neoplasm, with 2 etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC), with metformin therapy. This study aims to determine the association between metformin use and incident ESCC risk. METHODS: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015...
January 2020: American Journal of Gastroenterology
Mark A Preston, Anders H Riis, Vera Ehrenstein, Rodney H Breau, Julie L Batista, Aria F Olumi, Lorelei A Mucci, Hans-Olov Adami, Henrik T Sørensen
BACKGROUND: Metformin may decrease prostate cancer (PCa) risk by reducing hyperinsulinemia-associated carcinogenesis or through direct effects on cancer cells. OBJECTIVE: To evaluate the association between metformin use and PCa diagnosis. DESIGN, SETTING, AND PARTICIPANTS: We used the Danish Cancer Registry and the Aarhus University Prescription Database to conduct a nested case-control study among men residing in northern Denmark from 1989 to 2011...
December 2014: European Urology
Sil Kordes, Michael N Pollak, Aeilko H Zwinderman, Ron A Mathôt, Mariëtte J Weterman, Aart Beeker, Cornelis J Punt, Dick J Richel, Johanna W Wilmink
BACKGROUND: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication...
July 2015: Lancet Oncology
Ronac Mamtani, Nick Pfanzelter, Kevin Haynes, Brian S Finkelman, Xingmei Wang, Stephen M Keefe, Naomi B Haas, David J Vaughn, James D Lewis
OBJECTIVE: Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs). RESEARCH DESIGN AND METHODS: This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level...
July 2014: Diabetes Care
Jenny J Lin, Emily J Gallagher, Keith Sigel, Grace Mhango, Matthew D Galsky, Cardinale B Smith, Derek LeRoith, Juan P Wisnivesky
RATIONALE: Prior studies have shown an anticancer effect of metformin in patients with breast and colorectal cancer. It is unclear, however, whether metformin has a mortality benefit in lung cancer. OBJECTIVES: To compare overall survival of patients with diabetes with stage IV non-small cell lung cancer (NSCLC) taking metformin versus those not on metformin. METHODS: Using data from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 750 patients with diabetes 65-80 years of age diagnosed with stage IV NSCLC between 2007 and 2009...
February 15, 2015: American Journal of Respiratory and Critical Care Medicine
Hee Jeong Kim, Hyunwook Kwon, Jong Won Lee, Hwa Jung Kim, Sae Byul Lee, Hee Sung Park, Guiyun Sohn, Yura Lee, Beom Seok Koh, Jong Han Yu, Byung Ho Son, Sei Hyun Ahn
INTRODUCTION: Metformin use has recently been observed to decrease both the rate and mortality of breast cancer. Our study was aim to determine whether metformin use is associated with survival in diabetic breast cancer patients by breast cancer subtype and systemic treatment. METHODS: Data from the Asan Medical Center Breast Cancer Database from 1997 to 2007 were analyzed. The study cohort comprised 6,967 nondiabetic patients, 202 diabetic patients treated with metformin, and 184 diabetic patients that did not receive metformin...
May 3, 2015: Breast Cancer Research: BCR
Bruce B Duncan, Maria I Schmidt
No abstract text is available yet for this article.
September 2009: Diabetes Care
Barbara Salani, Alberto Del Rio, Cecilia Marini, Gianmario Sambuceti, Renzo Cordera, Davide Maggi
Metformin is the first-line treatment for type 2 diabetes. Results from several clinical studies have indicated that type 2 diabetic patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once it has entered the cell through organic cation transporters, metformin decreases mitochondrial respiration chain activity and ATP production that, in turn, activates AMP-activated protein kinase, which regulates energy homeostasis...
2014: Endocrine-related Cancer
Silvio E Inzucchi, David Fitchett, Dubravka Jurišić-Eržen, Vincent Woo, Stefan Hantel, Christina Janista, Stefan Kaspers, Jyothis T George, Bernard Zinman
AIMS: In the EMPA-REG OUTCOME® trial, the sodium-glucose cotransporter 2 inhibitor empagliflozin when given in addition to standard care improved cardiovascular (CV) and renal outcomes, and reduced mortality. Trial participants were on a variety of glucose-lowering therapies at baseline, some of which could potentially affect CV risk. This analysis investigated whether the use of background diabetes therapy affected the risk of CV death, hospitalizations for heart failure, and progression of chronic kidney disease, among patients treated with empagliflozin...
April 2020: Diabetes, Obesity & Metabolism
Nisa M Maruthur, Eva Tseng, Susan Hutfless, Lisa M Wilson, Catalina Suarez-Cuervo, Zackary Berger, Yue Chu, Emmanuel Iyoha, Jodi B Segal, Shari Bolen
BACKGROUND: Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices. PURPOSE: To evaluate the comparative effectiveness and safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists) and selected metformin-based combinations in adults with type 2 diabetes...
June 7, 2016: Annals of Internal Medicine
Son V Pham, Robert J Chilton
Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling...
July 1, 2017: American Journal of Cardiology
Atsushi Tanaka, Koichi Node
A growing body of evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors appear to be a powerful option to improve the cardiovascular (CV) prognosis in high CV-risk patients with type 2 diabetes. Despite a significant reduction in major adverse CV events with SGLT2 inhibitor treatment, however, an unexpected increased risk of amputation was observed in the CANVAS program and the subsequent pharmacovigilance analysis. Although the underlying mechanisms are currently unknown, because amputation has a large negative impact on patient clinical course, clinicians want to know the exact reason for the increased amputation in the canagliflozin treatment...
October 12, 2017: Cardiovascular Diabetology
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG ) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
Tushar Madaan, Mohd Akhtar, Abul Kalam Najmi
Diabetes mellitus is a disease that affects millions of people worldwide and its prevalence is estimated to rise in the future. Billions of dollars are spent each year around the world in health expenditure related to diabetes. There are several anti-diabetic drugs in the market for the treatment of non-insulin dependent diabetes mellitus. In this article, we will be talking about a relatively new class of anti-diabetic drugs called sodium glucose co-transporter 2 (SGLT2) inhibitors. This class of drugs has a unique mechanism of action focusing on inhibition of glucose reabsorption that separates it from other classes...
October 10, 2016: European Journal of Pharmaceutical Sciences
André J Scheen
Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug...
January 2015: Drugs
Paola Fioretto, Alberto Zambon, Marco Rossato, Luca Busetto, Roberto Vettor
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects...
August 2016: Diabetes Care
2016-10-20 01:23:41
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