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Metformin historical

Kristen A Marrone, Xian Zhou, Patrick M Forde, Michael Purtell, Julie R Brahmer, Christine L Hann, Ronan J Kelly, Barbara Coleman, Edward Gabrielson, Gary L Rosner, David S Ettinger
BACKGROUND: In the absence of a targeted oncogenic driver mutation or high programmed death-ligand 1 expression, systemic therapy with platinum-based doublet chemotherapy with or without bevacizumab has been the standard treatment in advanced or metastatic non-small cell lung cancer (NSCLC). Metformin has been shown to have antitumor effects via a variety of insulin-dependent and insulin-independent mechanisms and to be potentially synergistic with chemotherapy. MATERIALS AND METHODS: This open-label single-center phase II study (NCT01578551) enrolled patients with chemotherapy-naïve advanced or metastatic nonsquamous NSCLC and randomized them (3:1) to receive carboplatin, paclitaxel, and bevacizumab with (Arm A) or without (Arm B) concurrent metformin for four to six cycles followed by maintenance therapy with bevacizumab ± metformin continued until disease progression, intolerable toxicity, or study withdrawal...
February 27, 2018: Oncologist
Charles Kodner, Laurie Anderson, Katherine Pohlgeers
Glucose management in hospitalized patients poses challenges to physicians, including identifying blood glucose targets, judicious use of oral diabetes mellitus medications, and implementing appropriate insulin regimens. Uncontrolled blood glucose levels can lead to deleterious effects on wound healing, increased risk of infection, and delays in surgical procedures or discharge from the hospital. Previously recommended strict blood glucose targets for hospitalized patients result in more cases of hypoglycemia without improvement in patient outcomes...
November 15, 2017: American Family Physician
A H Hulst, J A W Polderman, E Ouweneel, A J Pijl, M W Hollmann, J H DeVries, B Preckel, J Hermanides
Historically, metformin was withheld before surgery for fear of metformin-associated lactic acidosis. Currently, however, this risk is deemed to be low and guidelines have moved towards the continuation of metformin. We hypothesized that continuing metformin peri-operatively would lower postoperative serum glucose level without an effect on plasma lactate levels. We performed a single-blind multicentre randomized controlled trial in people with type 2 diabetes mellitus scheduled for non-cardiac surgery and continued (MF+ group) or withheld (MF- group) metformin before surgery...
September 20, 2017: Diabetes, Obesity & Metabolism
Anish B Parikh, Peter Kozuch, Nicholas Rohs, Daniel J Becker, Benjamin P Levy
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity...
December 2017: Investigational New Drugs
William Kuan, Craig J Beavers, Maya E Guglin
Metformin remains a widely-used, first-line pharmacotherapy agent for patients with type 2 diabetes mellitus because of its efficacy, mild side effects, and affordability.However, use of this medication has traditionally been shunned by clinicians in patient populations that are considered at risk of lactic acidosis, such as those with heart failure. The underutilization of metformin can largely be attributed to the historical stigma of its biguanide predecessor, phenformin, and its association with lactic acidosis...
September 4, 2017: Heart Failure Reviews
Clifford J Bailey
Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin...
September 2017: Diabetologia
Wei-Sheng Lin, Jung-Hsin Lo, Jo-Hsuan Yang, Hao-Wei Wang, Shou-Zen Fan, Jui-Hung Yen, Pei-Yu Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. AIM OF THE STUDY: We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK)...
June 27, 2017: Journal of Ethnopharmacology
Anne Masich, Melissa E Badowski, Michelle D Liedtke, Patricia P Fulco
An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Laboratory parameters including serum creatinine (SCr), hemoglobin A1c (HgbA1c), plasma HIV RNA, CD4 cell count, and lactate were reviewed. Adverse drug reactions were assessed using patient-reported gastrointestinal intolerance and hypoglycemic symptoms...
October 2017: International Journal of STD & AIDS
Kasia J Lipska
No abstract text is available yet for this article.
February 7, 2017: Annals of Internal Medicine
Matthew J Crowley, Clarissa J Diamantidis, Jennifer R McDuffie, C Blake Cameron, John W Stanifer, Clare K Mock, Xianwei Wang, Shuang Tang, Avishek Nagi, Andrzej S Kosinski, John W Williams
Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment...
February 7, 2017: Annals of Internal Medicine
Connie M Rhee, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction...
2017: Nephron
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)...
February 2017: 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
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