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https://www.readbyqxmd.com/read/29779196/retrospective-analysis-of-an-insulin-to-liraglutide-switch-in-patients-with-type-2-diabetes-mellitus
#1
Eveline Bruinstroop, Laura Meyer, Catherine B Brouwer, Diana E van Rooijen, P Sytze van Dam
INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015)...
May 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29779024/a-randomized-clinical-trial-of-metformin-to-treat-autosomal-dominant-polycystic-kidney-disease
#2
Stephen L Seliger, Kaleab Z Abebe, Kenneth R Hallows, Dana C Miskulin, Ronald D Perrone, Terry Watnick, Kyongtae Tae Bae
BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways. Together these effects may reduce cyst growth in autosomal dominant polycystic kidney disease (ADPKD). METHODS: A phase II, double-blinded randomized placebo-controlled trial of 26 months duration. Participants will include nondiabetic adults (n = 96) aged 18-60 years, with an estimated glomerular filtration rate (eGFR) ≥50 mL/min/1...
May 18, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29777629/mechanisms-of-metformin-action-in-and-out-of-the-gut
#3
EDITORIAL
Takahiro Minamii, Munenobu Nogami, Wataru Ogawa
One hundred years have passed since guanidine, a precursor compound of biguanides and thus of metformin, was found to have a glucose-lowering effect in live animals1 . In this historical study, C. K. Watanabe1 did not set out to identify glucose-lowering agents but rather to understand the mechanism underlying the development of tetany in animals that have undergone parathyroidectomy. Watanabe 1 concluded that guanidine is a pathogenic factor responsible for tetany because its administration in rabbits resulted in "tetany-like" muscle cramps associated with low blood glucose levels...
May 19, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29777519/combination-glucose-lowering-therapy-plans-in-t2dm-case-based-considerations
#4
REVIEW
Lawrence Blonde, Susana Dipp, Daniel Cadena
Type 2 diabetes mellitus (T2DM) is a complex disease, and while lifestyle interventions remain the cornerstone of therapy, most patients will also require pharmacotherapy. Current diabetes treatment guidelines and algorithms recommend an individualized approach to setting glycemic goals and selecting treatment. Although a single antihyperglycemic agent may be appropriate as the initial T2DM pharmacotherapy, the progressive nature of the disease due to declining pancreatic β-cell function will result in the vast majority of T2DM patients eventually requiring two or more antihyperglycemic agents...
May 18, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29775878/repositioning-of-diabetes-treatments-for-depressive-symptoms-a-systematic-review-and-meta-analysis-of-clinical-trials
#5
REVIEW
Calum D Moulton, Christopher W P Hopkins, Khalida Ismail, Daniel Stahl
Depression is a common comorbidity in diabetes but conventional antidepressant treatments do not consistently improve outcomes. We tested whether established diabetes treatments can also improve depressive symptoms and examined biological correlates of response. We performed a multi-database systematic search of all clinical trials, which measured the effect of licensed diabetes treatments on depressive symptoms using a validated questionnaire. Results of randomised controlled trials (RCT's) were pooled for meta-analysis...
May 7, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29774060/metformin-prevents-nerve-growth-factor-dependent-proliferative-and-proangiogenic-effects-in-epithelial-ovarian-cancer-cells-and-endothelial-cells
#6
Maritza P Garrido, Carolina Vera, Margarita Vega, Andrew F G Quest, Carmen Romero
Background: Epithelial ovarian cancer (EOC) is characterized by exacerbated angiogenesis regulated by proangiogenic and growth factors. Nerve growth factor (NGF) is overexpressed in EOC where it promotes proliferation as well as survival and is considered a proangiogenic factor. Metformin, a drug commonly used in the treatment of diabetes, is attributed to antineoplastic effects, but the underlying mechanisms remain unknown. Given that current therapies yield modest results in EOC patients, the aim of this study was to determine the effects of metformin on NGF-enhanced proliferation of EOC cells and the angiogenic potential of endothelial cells...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29773079/effects-of-linagliptin-on-endothelial-function-and-postprandial-lipids-in-coronary-artery-disease-patients-with-early-diabetes-a-randomized-placebo-controlled-double-blind-trial
#7
Norbert J Tripolt, Felix Aberer, Regina Riedl, Jasmin Url, Gudrun Dimsity, Andreas Meinitzer, Tatjana Stojakovic, Faisal Aziz, Ronald Hödl, Gabriele Brachtl, Dirk Strunk, Marianne Brodmann, Franz Hafner, Harald Sourij
BACKGROUND: Early glucose lowering intervention in subjects with type 2 diabetes mellitus was demonstrated to be beneficial in terms of micro- and macrovascular risk reduction. However, most of currently ongoing cardiovascular outcome trials are performed in subjects with manifest atherosclerosis and long-standing diabetes. Therefore, the aim of this study is to investigate the effects of the dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements...
May 17, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29772687/metformin-induces-apoptosis-and-alters-cellular-responses-to-oxidative-stress-in-ht29-colon-cancer-cells-preliminary-findings
#8
Paola Sena, Stefano Mancini, Marta Benincasa, Francesco Mariani, Carla Palumbo, Luca Roncucci
Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anti-cancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM for 24/48 h. We performed immunofluorescence experiments by means of confocal microscopy and western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770821/a-size-shrinkable-nanoparticle-based-combined-anti-tumor-and-anti-inflammatory-strategy-for-enhanced-cancer-therapy
#9
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29770171/risk-of-gastric-cancer-development-after-eradication-of-helicobacter-pylori
#10
REVIEW
Ka-Shing Cheung, Wai K Leung
Helicobacter pylori ( H. pylori ) infection is the most important risk factor for gastric cancer (GC) development through the Correa's gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate GC, as pre-neoplastic lesions (atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing (serum pepsinogen) can predict the risk of atrophic gastritis...
May 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29769766/fenugreek-diabetes-and-periodontal-disease-a-cross-link-of-sorts
#11
Gopalakrishnan Sundaram, Theyagarajan Ramakrishnan, Harinath Parthasarathy, Manoj Raja, Samuel Raj
Aims: The aim of this study was to observe the sequelae of fenugreek adjunctive to nonsurgical periodontal therapy and its comparison to a group treated with scaling and root planing (SRP) and metformin alone by assessing their respective effects on periodontal parameters, glycemic status, and serum lipid levels. Materials and Methods: The study comprised eighty patients who were further divided into two groups. Each group consisted of 40 patients. Group 1 consisted of uncontrolled noninsulin-dependent diabetes mellitus (NIDDM) patients with chronic generalized periodontitis, who received SRP and treatment with metformin...
March 2018: Journal of Indian Society of Periodontology
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#12
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764225/initial-combination-therapy-with-vildagliptin-plus-metformin-in-drug-na%C3%A3-ve-patients-with-t2dm-a-24-week-real-life-study-from-asia
#13
Manoj Chawla, Tae Ho Kim, Roberto C Mirasol, Pathan Faruque, Kathryn Cooke, Peggy Hours-Zesiger, Abhijit Shete
AIMS: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). METHODS: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29764222/comparative-efficacy-of-once-weekly-semaglutide-and-sglt-2-inhibitors-in-type-2-diabetic-patients-inadequately-controlled-with-metformin-monotherapy-a-systematic-literature-review-and-network-meta-analysis
#14
Rohini Sharma, Lars Wilkinson, Hrvoje Vrazic, Evan Popoff, Sandra Lopes, Steve Kanters, Eric Druyts
OBJECTIVE: Treatment intensification with additional antidiabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin. METHODS: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29763426/environmental-concentrations-of-metformin-exposure-affect-aggressive-behavior-in-the-siamese-fighting-fish-betta-splendens
#15
Ronald David MacLaren, Kathryn Wisniewski, Christina MacLaren
Metformin, the medicine most commonly prescribed for treatment of Type II diabetes, is among the most abundant pharmaceuticals being introduced into the environment. Pharmaceuticals are increasingly found in wastewater and surface waters around the world, often due to incomplete metabolism in humans and subsequent excretion in human waste. Risk analyses and exposure studies have raised concerns about potential negative impacts of pharmaceuticals at current environmental levels. Results of the present study indicate that metformin at concentrations in the range of what has been documented in freshwater systems and waste-water effluent (40 μg/L) affects aggressive behavior in adult male Betta splendens...
2018: PloS One
https://www.readbyqxmd.com/read/29762853/caffeine-induces-metformin-anticancer-effect-on-fibrosarcoma-in-hamsters
#16
D J Popović, D Lalošević, D Miljković, K J Popović, I Čapo, J K Popović
OBJECTIVE: We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. MATERIALS AND METHODS: 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29762537/the-cardioprotective-effect-of-metformin-in-doxorubicin-induced-cardiotoxicity-the-role-of-autophagy
#17
Rita Zilinyi, Attila Czompa, Andras Czegledi, Andrea Gajtko, Dora Pituk, Istvan Lekli, Arpad Tosaki
The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague⁻Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally...
May 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29761830/itc-commentary-on-metformin-clinical-drug-drug-interaction-study-design-that-enables-an-efficacy-and-safety-based-dose-adjustment-decision
#18
Maciej J Zamek-Gliszczynski, Xiaoyan Chu, Jack A Cook, Joseph M Custodio, Aleksandra Galetin, Kathleen M Giacomini, Caroline A Lee, Mary F Paine, Adrian S Ray, Joseph A Ware, Matthias B Wittwer, Lei Zhang
Metformin drug-drug interaction (DDI) studies are conducted during development of drugs that inhibit organic cation transporters and/or multidrug and toxin extrusion proteins (OCTs/MATEs). Monitoring solely changes in systemic exposure, the typical DDI study endpoint appears inadequate for metformin, which is metabolically stable, has poor passive membrane permeability, and undergoes transporter-mediated tissue distribution and clearance. Evaluation of renal clearance, antihyperglycemic effects, and potentially lactate as an exploratory safety marker, can support rational metformin dose adjustment...
May 15, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29761175/anti-tumoral-effects-of-exercise-on-hepatocellular-carcinoma-growth
#19
Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V St-Pierre, Jean-François Dufour
Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups...
May 2018: Hepatology communications
https://www.readbyqxmd.com/read/29760945/liraglutide-and-dulaglutide-therapy-in-addition-to-sglt-2-inhibitor-and-metformin-treatment-in-indian-type-2-diabetics-a-real-world-retrospective-observational-study
#20
S Ghosal, B Sinha
Background: Therapy for Type 2 diabetes (T2D) has been transformed by the introduction of newer agents like Glucagon like Peptide Receptor Agonists (GLP-1RA) and Sodium-glucose linked transporter inhibitors (SGLT2i). However with co-initiation of SGLT2i and GLP-1RA in the DURATION 8 trial an improvement in HbA1c was noted but the beneficial effect was not equal to the sum of its parts. In view of this we proceeded to test the hypothesis that sequential addition of GLP-1RA therapy to metformin and SGLT-2i may be more beneficial...
2018: Clinical Diabetes and Endocrinology
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