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Metformin AND GLP-1

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https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#1
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
March 23, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#2
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28294499/a-placebo-controlled-randomised-trial-of-the-addition-of-once-weekly-glp-1-receptor-agonist-dulaglutide-to-titrated-daily-insulin-glargine-in-patients-with-type-2-diabetes-award-9
#3
Paolo Pozzilli, Paul Norwood, Esteban Jodar, Melanie J Davies, Tibor Ivanyi, Honghua Jiang, Brad Woodward, Zvonko Milicevic
AIMS: Compare the addition of weekly dulaglutide versus the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimal HbA1c . METHODS: Patients (N = 300) from this Phase 3, double-blind, parallel-arm, placebo-controlled study were randomised to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± SD baseline dose: 39 ± 22 U), with or without metformin (≥1,500 mg/day)...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28283565/assessment-of-pancreas-safety-in-the-development-program-of-once-weekly-glp-1-receptor-agonist-dulaglutide
#4
Michael A Nauck, Jean-Louis Frossard, Jamie S Barkin, Greg Anglin, Ingrid E Hensley, Kristine D Harper, Zvonko Milicevic
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks...
March 10, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#5
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#6
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
February 13, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28274140/dulaglutide-for-the-treatment-of-type-2-diabetes
#7
André J Scheen
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising with the development of once weekly compounds and the demonstration of a potential reduction in cardiorenal outcomes. Areas covered: The paper describes the main pharmacokinetic/pharmacodynamic characteristics of dulaglutide, a new once-weekly GLP-1 RA. Dulaglutide was extensively investigated in the phase-3 AWARD program, which demonstrated its safety and efficacy when compared to placebo or active glucose-lowering agents in patients treated with diet alone, metformin or sulfonylurea monotherapy, oral dual therapies and basal insulin...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28224463/liraglutide-versus-lixisenatide-long-term-cost-effectiveness-of-glp-1-receptor-agonist-therapy-for-the-treatment-of-type-2-diabetes-in-spain
#8
Pedro Mezquita-Raya, Antonio Ramírez de Arellano, Nana Kragh, Gabriela Vega-Hernandez, Johannes Pöhlmann, William J Valentine, Barnaby Hunt
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists are used successfully in the treatment of patients with type 2 diabetes as they are associated with low hypoglycemia rates, weight loss and improved glycemic control. This study compared, in the Spanish setting, the cost-effectiveness of liraglutide 1.8 mg versus lixisenatide 20 μg, both GLP-1 receptor agonists, for patients with type 2 diabetes who had not achieved glycemic control targets on metformin monotherapy. METHODS: The IMS CORE Diabetes Model was used to project clinical outcomes and costs, expressed in 2015 Euros, over patient lifetimes...
February 21, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28188972/effect-of-exercise-combined-with-glucagon-like-peptide-1-receptor-agonist-treatment-on-cardiac-function-a-randomised-double-blinded-placebo-controlled-clinical-trial
#9
Peter G Jørgensen, Magnus T Jensen, Pernille Mensberg, Heidi Storgaard, Signe Nyby, Jan S Jensen, Filip K Knop, Tina Vilsbøll
In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo combined with supervised exercise in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (-7.1 ± 1.6 cm/s (mean ± standard deviation) to -7...
February 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28161303/comparison-of-exenatide-and-acarbose-on-intra-abdominal-fat-content-in-patients-with-obesity-and-type-2-diabetes-a-randomized-controlled-trial
#10
Li Shi, Jing Zhu, Ping Yang, Xiaoqiang Tang, Wenlong Yu, Changjie Pan, Moyu Shen, Dalong Zhu, Jinluo Cheng, Xinhua Ye
OBJECTIVE: To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. METHODS: This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months...
February 1, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28145471/synergistic-effects-of-metformin-with-liraglutide-against-endothelial-dysfunction-through-glp-1-receptor-and-pka-signalling-pathway
#11
Jing Ke, Ye Liu, Jin Yang, Ran Lu, Qing Tian, Wenfang Hou, Guang Wang, Rui Wei, Tianpei Hong
Metformin or glucagon-like peptide-1 (GLP-1) analogue liraglutide has cardiovascular benefits. However, it is not clear whether their combined treatment have additive or synergistic effects on the vasculature. In this study, human umbilical vein endothelial cells (HUVECs), exposed to palmitic acid (PA) to induce endothelial dysfunction, were incubated with metformin, liraglutide or their combination. High fat diet (HFD)-fed ApoE(-/-) mice were randomized into control, metformin, liraglutide, and combination treatment groups...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143456/short-term-effectiveness-of-low-dose-liraglutide-in-combination-with-metformin-versus-high-dose-liraglutide-alone-in-treatment-of-obese-pcos-randomized-trial
#12
RANDOMIZED CONTROLLED TRIAL
Mojca Jensterle, Nika Aleksandra Kravos, Katja Goričar, Andrej Janez
BACKGROUND: Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. METHODS: Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m(2)) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1...
January 31, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28133970/lixisenatide
#13
Delilah McCarty, Megan Coleman, Cassie L Boland
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the glucagon-like peptide-1 receptor agonist (GLP-1RA), lixisenatide, in the treatment of type 2 diabetes mellitus. DATA SOURCES: A PubMed (1966-2016) search was conducted using the following keywords: lixisenatide, AVE0010, glucagon-like peptide-1 agonist, and type 2 diabetes. References were reviewed to identify additional sources. STUDY SELECTION AND DATA EXTRACTION: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, or safety of lixisenatide in human subjects...
January 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28127851/impact-of-insulin-sensitivity-beta-cell-function-and-glycemic-control-on-initiation-of-second-line-glucose-lowering-treatment-in-newly-diagnosed-type-2-diabetes
#14
Wolfgang Rathmann, Klaus Strassburger, Brenda Bongaerts, Pavel Bobrov, Oliver Kuss, Karsten Müssig, Daniel F Markgraf, Julia Szendroedi, Christian Herder, Michael Roden
AIMS: The aim was to investigate whether insulin sensitivity, beta-cell function or glycemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. MATERIAL AND METHODS: Type 2 diabetes patients (n = 138) on initial metformin monotherapy (age [mean ± SD]: 52 ± 10 years; 67% males; BMI: 32 ± 6 kg/m(2) ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under treatment of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp: M value; i...
January 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28124822/liraglutide-effects-on-beta-cell-insulin-sensitivity-and-glucose-effectiveness-in-patients-with-stable-coronary-artery-disease-and-newly-diagnosed-type-2-diabetes
#15
Christian Anholm, Preman Kumarathurai, Lene Rørholm Pedersen, Olav Wendelboe Nielsen, Ole Peter Kristiansen, Mogens Fenger, Sten Madsbad, Ahmad Sajadieh, Steen Bendix Haugaard
AIMS: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Design: A randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM...
January 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-non-alcoholic-fatty-liver-disease-with-type-2-diabetes-mellitus
#16
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28003008/glucagon-like-peptide-1-glp-1-receptor-agonists-in-the-treatment-of-obese-women-with-polycystic-ovary-syndrome
#17
Themistoklis Tzotzas, Spyridon N Karras, Niki Katsiki
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females and is often associated with a number of cardiometabolic disorders such as central obesity, dyslipidaemia, hypertension, insulin resistance, hyperinsulinaemia, glucose intolerance and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a gut hormone secreted after a meal, enhances glucose-stimulated insulin secretion and additionally suppresses appetite and gastric motility. Most studies found impaired GLP-1 kinetics in obese individuals, whereas small studies in PCOS reported reduced, normal or even elevated GLP-1 levels...
December 21, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27998910/pancreatic-effects-of-liraglutide-or-sitagliptin-in-overweight-patients-with-type-2-diabetes-a-12-week-randomized-placebo-controlled-trial
#18
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Indra C Pieters-van den Bos, Karuna E W Vendrik, Trynke Hoekstra, Marco J Bruno, Michaela Diamant, Daniël H van Raalte, Djuna L Cahen
OBJECTIVE: To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology. RESEARCH DESIGN AND METHODS: For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n = 19), sitagliptin 100 mg (n = 19), or matching placebos (n = 17) once daily for 12 weeks...
March 2017: Diabetes Care
https://www.readbyqxmd.com/read/27943107/the-efficacy-of-ideglira-insulin-degludec-liraglutide-combination-in-adults-with-type-2-diabetes-inadequately-controlled-with-a-glp-1-receptor-agonist-and-oral-therapy-dual-iii-randomized-clinical-trial
#19
Sultan Linjawi, Bruce W Bode, Louis B Chaykin, Jean-Pierre Courrèges, Yehuda Handelsman, Lucine M Lehmann, Abhishek Mishra, Richard W Simpson
INTRODUCTION: The progressive nature of type 2 diabetes necessitates treatment intensification. This often involves intensification with oral antidiabetic drugs (OADs) initially, followed by other agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with the majority of patients eventually requiring insulin therapy. Therefore, this trial aimed to investigate the efficacy of IDegLira (combination of insulin degludec and liraglutide) in controlling glycemia in adults with type 2 diabetes who were inadequately controlled on a GLP-1RA and OADs...
February 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#20
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
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