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Metformin historical

Randy Strong, Richard A Miller, Adam Antebi, Clinton M Astle, Molly Bogue, Martin S Denzel, Elizabeth Fernandez, Kevin Flurkey, Karyn L Hamilton, Dudley W Lamming, Martin A Javors, João Pedro de Magalhães, Paul Anthony Martinez, Joe M McCord, Benjamin F Miller, Michael Müller, James F Nelson, Juliet Ndukum, G Ed Rainger, Arlan Richardson, David M Sabatini, Adam B Salmon, James W Simpkins, Wilma T Steegenga, Nancy L Nadon, David E Harrison
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously...
October 2016: Aging Cell
K Kalinsky, T Zheng, H Hibshoosh, X Du, P Mundi, J Yang, S Refice, S M Feldman, B Taback, E Connolly, K D Crew, M A Maurer, D L Hershman
PURPOSE: Reverse Phase Protein Array (RPPA) is a high-throughput antibody-based technique to assess cellular protein activity. The goal of this study was to assess protein marker changes by RPPA in tumor tissue from a pre-surgical metformin trial in women with operable breast cancer (BC). METHODS: In an open-label trial, metformin 1500-mg PO daily was administered prior to resection in 35 non-diabetic patients with stage 0-III BC, body mass index ≥25 kg/m(2)...
June 15, 2016: Clinical & Translational Oncology
Lisa M Younk, Elizabeth M Lamos, Stephen N Davis
INTRODUCTION: Cardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes. AREAS COVERED: Findings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors will be reviewed...
September 2016: Expert Opinion on Drug Safety
Leslie Hazel-Fernandez, Yihua Xu, Chad Moretz, Yunus Meah, Jean Baltz, Jean Lian, Edward Kimball, Jonathan Bouchard
OBJECTIVE: To describe treatment regimen changes of patients with type 2 diabetes mellitus (T2DM) initiating metformin monotherapy, and assess factors associated with those changes 12 months post-initiation. METHODS: Retrospective cohort analysis of medical, pharmacy and laboratory claims of 17,527 Medicare Advantage (MAPD) Humana members aged 18-89, who had ≥1 medical claim with primary diagnosis or ≥2 medical claims with secondary diagnosis of T2DM (ICD-9-CM code 250...
2015: Current Medical Research and Opinion
Prasarn Manitpisitkul, Christopher R Curtin, Kevin Shalayda, Shean-Sheng Wang, Lisa Ford, Donald Heald
OBJECTIVE: To investigate potential drug-drug interactions between topiramate and metformin and pioglitazone at steady state. METHODS: Two open-label studies were performed in healthy adult men and women. In Study 1, eligible participants were given metformin alone for 3 days (500 mg twice daily [BID]) followed by concomitant metformin and topiramate (titrated to 100mg BID) from days 4 to 10. In Study 2, eligible participants were randomly assigned to treatment with pioglitazone 30 mg once daily (QD) alone for 8 days followed by concomitant pioglitazone and topiramate (titrated to 96 mg BID) from days 9 to 22 (Group 1) or to topiramate (titrated to 96 mg BID) alone for 11 days followed by concomitant pioglitazone 30 mg QD and topiramate 96 mg BID from days 12 to 22 (Group 2)...
November 2014: Epilepsy Research
Kevin Kalinsky, Katherine D Crew, Susan Refice, Tong Xiao, Antai Wang, Sheldon M Feldman, Bret Taback, Aqeel Ahmad, Serge Cremers, Hanina Hibshoosh, Matthew Maurer, Dawn L Hershman
INTRODUCTION: We conducted a presurgical trial to assess the tissue-related effects of metformin in overweight/obese breast cancer (BC) patients. METHODS: Metformin 1,500 mg daily was administered to 35 nondiabetics with stage 0-III BC, body mass index (BMI) ≥ 25 kg/m(2). The primary endpoint was tumor proliferation change (i.e., ki-67). Tumor proliferation change was compared to untreated historical controls, matched by age, BMI, and stage. RESULTS: There was no reduction in ln(ki-67) after metformin (p = ...
May 2014: Cancer Investigation
Ting-Yu Wang, Tewodros Eguale, Robyn Tamblyn
BACKGROUND: Given the high prevalence of diabetes, guidelines are updated frequently to reflect optimal treatment recommendations. Our study aims to measure the response of primary care physicians to changes in choice of initial therapy for patients with type 2 diabetes in relationship to a change in Canadian Diabetes Association (CDA) Guidelines in 2008. We also assessed patients' and physicians' factors which may affect this change. METHODS: Historical cohort study of primary care physicians' participating in an electronic medical record research network in Quebec, Canada...
2013: BMC Health Services Research
E L Lamos, S A Stein, S N Davis
Insulin secretagogue therapy is commonly used in clinical practice. These agents may be utilized as first, second-line or adjunct therapy behind metformin for treatment of type 2 diabetes mellitus. Sulfonylureas and meglitinides are effective treatments, but cumulative data over decades of research raise concerns regarding universal prescribing. The role of insulin secretagogue therapy in β-cell failure, blunting of ischemic pre-conditioning, the incidence of hypoglycemia - specifically in at-risk populations, modest weight gain and the unproven link to cancer are discussed...
September 2013: Panminerva Medica
Brendan J Quinn, Hiroshi Kitagawa, Regan M Memmott, Joell J Gills, Phillip A Dennis
Metformin is the most commonly prescribed drug for type 2 diabetes (T2DM). Retrospective studies show that metformin is associated with decreased cancer risk. This historical correlation has driven vigorous research campaigns to determine the anticancer mechanisms of metformin. Consolidating the preclinical data is a challenge because unanswered questions remain concerning relevant mechanisms, bioavailability, and genetic factors that confer metformin sensitivity. Perhaps the most important unanswered question is whether metformin has activity against cancer in non-diabetics...
September 2013: Trends in Endocrinology and Metabolism: TEM
Razia Petkar, Neil Wright
Childhood overweight and obesity are increasingly common management problems for clinicians. This review focuses on the pharmacological management of obesity in children. It considers historical treatments, the options currently available (principally orlistat and metformin) and some potential future therapeutic interventions. The short term psychological effect of obesity and longer term health impact are discussed. The clinical settings in which drug treatment may be appropriate, the importance of lifestyle interventions, and the evidence and clinical guidance that underpin their use are discussed...
June 2013: Archives of Disease in Childhood. Education and Practice Edition
Michael Berk
There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents...
2012: BMC Medicine
Jayabharathi Vaidyanathan, Sally Choe, Chandrahas G Sahajwalla
Type 2 diabetes results when insulin secretion is unable to keep the plasma glucose levels as per acceptable range. This leads to chronic hyperglycemia and its associated microvascular complications such as renal impairment (diabetic nephropathy), retinal abnormalities (diabetic retinopathy), and autonomic, sensory, and motor neuropathies (diabetic neuropathy) and macrovascular disease. Historically, type 2 diabetes is well known as an adult-onset disease; however, lately, the incidence of the disease is reported to be increasing in children...
May 2012: Journal of Pharmaceutical Sciences
Andreas E Buchs, Barbara G Silverman
It has been hypothesized that incidence of and mortality from several malignancies are increased among diabetic patients. Whether certain treatment modalities, including use of metformin, sulfonylureas, or insulins, affect cancer incidence or mortality and whether use of long-acting insulin analogues glargine and detemir may increase cancer incidence more than traditional human insulins are debated. The objective was to investigate the association between specific glucose-lowering agents and cancer incidence in diabetic members of an Israeli health maintenance organization...
October 2011: Metabolism: Clinical and Experimental
Stanley H Hsia, Maria D Navar, Petra Duran, Magda Shaheen, Mayer B Davidson
OBJECTIVE: To compare sitagliptin and thiazolidinediones as third-line oral antihyperglycemic agents among ethnic minority patients with poorly controlled type 2 diabetes mellitus. METHODS: In an open-label, single-arm design, we treated type 2 diabetic patients who had suboptimal diabetes control on maximum tolerated dosages of metformin plus sulfonylureas with the addition of sitagliptin, 100 mg daily, and compared their responses with findings from a historical control group of similar patients treated with rosiglitazone, 8 mg daily, or pioglitazone, 45 mg daily, as their third-line oral agent...
September 2011: Endocrine Practice
Gyula Petrányi, Mária Zaoura-Petrányi
UNLABELLED: Treatment with metformin three times 500 mg daily had been advised since 2002, to patients suffering from the polycystic ovary syndrome diagnosed by the Rotterdam criteria and who did not want to take contraceptive pills. More recently, life style changes have also been introduced to treatment recommendation: increased physical activity, low glycaemic index diet; also with calorie restriction for the obese patients. AIM: To assess the efficacy of the two treatment forms on clinical symptoms of the disease...
April 17, 2011: Orvosi Hetilap
Berhane Seyoum
INTRODUCTION: The historical background of the discovery of incretins became of particular interest when insulin response was found to be much more pronounced when glucose was given orally, rather than intravenously. The robust insulin secretion seen in response to oral glucose, as opposed to intravenous glucose, is due to incretin hormones. Since the discovery of incretins, the significance of sitagliptin and metformin combination therapy has become an essential strategy in combating diabetes...
March 2011: Expert Opinion on Pharmacotherapy
Nawaporn Numbenjapon, Pairunyar Nakavachara, Jeerunda Santiprabhob, Pornpimol Kiattisakthavee, Renu Wongarn, Supawadee Likitmaskul
BACKGROUND: Childhood obesity is an emerging national health problem in Thailand. Our previous study found that one third of obese children and adolescents had impaired glucose tolerance (IGT) and 2.6 percent had already developed type 2 diabetes mellitus. An immediate strategy needs to be established in order to improve these metabolic problems. OBJECTIVE: To determine whether diet and exercise education for lifestyle modification with or without metformin therapy in our diabetes clinic is enable to improve these metabolic problems...
November 2010: Journal of the Medical Association of Thailand, Chotmaihet Thangphaet
Jude U Ohaeri, Abayomi O Akanji
The concept of metabolic syndrome in psychiatry provides a united front for confronting a series of metabolic changes that are predictive of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which are highly prevalent in severe mental disorders (SMDs), such as schizophrenia, bipolar disorders, and severe depression. This review attempts to answer the following questions: (1) Is there evidence of significantly increased risk of metabolic syndrome in SMDs? (2) How is this evidence explained by stress theory and functional polymorphism? (3) What role can psychopharmacology and psychosocial therapies play in minimizing the problem? We have done a historical review using related literature from Medline...
April 2011: Metabolic Syndrome and related Disorders
Scott V Monte, Jerome J Schentag, Martin H Adelman, Joseph A Paladino
BACKGROUND: For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose...
March 2010: Journal of Diabetes Science and Technology
O Zolk
The identification of transporters for organic cations involved in the distribution and elimination of the antidiabetic compound metformin marks a milestone in the study of metformin's pharmacokinetics. This was followed by the urgent question of whether genetic variations in these transporters can affect efficacy and risk of adverse events associated with metformin use. After a brief historical review of the discovery of the transporters for cationic drugs, the pharmacogenetics of metformin is discussed here in the light of recent literature...
December 2009: Clinical Pharmacology and Therapeutics
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