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Susan L Samson, Alan J Garber
Incretin-based therapies are important addition to our armamentarium for the treatment of type 2 diabetes (T2DM). There are six Glucagon-like peptide-1 receptor agonists (GLP-1RAs) which have received regulatory approval for clinical use. The short-acting GLP-1RAs include exenatide twice daily, liraglutide once daily, and lixisenatide once daily. The approved long-acting GLP-1RAs are administered weekly and are exenatide, albiglutide, and dulaglutide. Although all of these therapies lower hemoglobin A1C (HbA1C), there also are unique features of GLP-1RAs that have been made manifest from clinical trial data with regard to weight-loss efficacy, fasting and post-prandial glucose control, cardiovascular safety and protection, and gastrointestinal and injection adverse effects...
December 2016: Current Diabetes Reports
Marc S Rendell
Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. Area covered: The pharmacokinetic and pharmacodynamic properties of albiglutide and its clinical effects are discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents. Expert opinion: Albiglutide has a chemical structure quite distinct from that of other marketed GLP-1 RAs. The agent has less gastrointestinal side effects than other comparable GLP-1 RAs and is safe in patients with renal failure...
October 3, 2016: Expert Opinion on Biological Therapy
Jamie Wroge, Nancy Toedter Williams
OBJECTIVE: To evaluate the literature about the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of cardiac disorders, specifically myocardial infarction (MI) and heart failure (HF). DATA SOURCES: Searches were conducted in MEDLINE (1946-May 2016) and Excerpta Medica (1980-May 2016) using EMBASE with the search terms glucagon-like peptide 1, exenatide, albiglutide, liraglutide, dulaglutide, myocardial infarction, heart failure, and cardiovascular The references of relevant articles were reviewed to identify additional citations...
August 16, 2016: Annals of Pharmacotherapy
Devada Singh-Franco, Catherine Harrington, Eglis Tellez-Corrales
OBJECTIVE: This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis. METHODS: In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. RESULTS: There were 2261 participants, 49-79 years of age, 49% men and 44% Caucasians...
2016: SAGE Open Medicine
Kira B Harris, Cassie L Boland
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well...
September 2016: Pharmacotherapy
X Xue, Z Ren, A Zhang, Q Yang, W Zhang, F Liu
BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in the treatment of type 2 diabetes. Herein, we compared the efficacy and safety of once-weekly GLP-1RAs with exenatide and liraglutide separately. METHODS: We systematically surveyed the pertinent literature using various databases. The randomised controlled trials that compared once-weekly GLP-1RAs with exenatide and liraglutide in type 2 diabetes were included...
August 2016: International Journal of Clinical Practice
Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin...
2016: Clinical Pharmacology: Advances and Applications
Z X Li, S S Wu, Z R Yang, S Y Zhan, F Sun
OBJECTIVE: To systematically review the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on two common respiratory system adverse events (RSAE: nasopharyngitis and upper respiratory tract infection) among type 2 diabetes (T2DM). METHODS: Medline, Embase, Clinical trials and Cochrane library were searched from inception through May 2015 to identify randomized clinical trials(RCTs) assessed safety of GLP-1RAs versus placebo or other anti-diabetic drugs in T2DM...
June 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Alan A Martin, Daniel Parks
No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide-1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Kristin M Janzen, Taylor D Steuber, Sarah A Nisly
OBJECTIVE: To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). DATA SOURCES: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus STUDY SELECTION AND DATA EXTRACTION: All English-language trials that examined glycemic end points using GLP-1 agonists in humans with T1DM were included...
August 2016: Annals of Pharmacotherapy
Zhixia Li, Yuan Zhang, Xiaochi Quan, Zhirong Yang, Xiantao Zeng, Linong Ji, Feng Sun, Siyan Zhan
OBJECTIVE: To synthesize current evidence of the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment discontinuation and glycemic level in patients with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Literature search (Medline, Embase, the Cochrane library), website of clinical trial, bibliographies of published systematic reviews. ELIGIBILITY CRITERIA: Randomized controlled trials with available data comparing GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2 diabetes...
2016: PloS One
L A Leiter, J M Mallory, T H Wilson, R R Reinhardt
Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes mellitus. The GI safety of albiglutide, a once-weekly GLP-1RA, was assessed using data from five phase III studies. In a pooled analysis of four placebo-controlled trials, the most common GI AEs were diarrhoea (albiglutide, 14.5% vs. placebo, 11.5%) and nausea (albiglutide, 11.9% vs. placebo, 10.3%), with most patients experiencing 1-2 events...
September 2016: Diabetes, Obesity & Metabolism
Jessica E Matthews, Rickey R Reinhardt, Molly C Carr
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) vary in their structure, duration of action, efficacy, and safety. In order to optimize glycemic control, it is important to target both fasting (FPG) and postprandial plasma (PPG) glucose. Although phase 3 trials document the effect of GLP-1 RAs on glycated hemoglobin, few data are available to assess their effect on PPG. Albiglutide is a once-weekly GLP-1 RA with a half-life of ≈ 5 days. The goal of this review is to summarize the effects of albiglutide on PPG in four phase 2 trials and to describe the PPG-lowering effects of the GLP-1 RAs...
May 2016: Postgraduate Medicine
Sanjay Kalra, Manash P Baruah, Rakesh K Sahay, Ambika Gopalakrishnan Unnikrishnan, Shweta Uppal, Omolara Adetunji
Glucagon-like peptide-1 (GLP-1)-based therapy improves glycaemic control through multiple mechanisms, with a low risk of hypoglycaemia and the additional benefit of clinically relevant weight loss. Since Starling and Bayliss first proposed the existence of intestinal secretions that stimulate the pancreas, tremendous progress has been made in the area of incretins. As a number of GLP-1 receptor agonists (GLP-1 RAs) continue to become available, physicians will soon face the challenge of selecting the right option customized to their patient's needs...
March 2016: Indian Journal of Endocrinology and Metabolism
John J Lepore, Eric Olson, Laura Demopoulos, Thomas Haws, Zixing Fang, April M Barbour, Michael Fossler, Victor G Davila-Roman, Stuart D Russell, Robert J Gropler
OBJECTIVES: This study sought to determine if glucagon-like peptide (GLP)-1 ameliorates myocardial metabolic abnormalities in chronic heart failure. BACKGROUND: Albiglutide (GSK716155) is a GLP-1 agonist indicated for type 2 diabetes. METHODS: We performed a randomized, placebo-controlled study evaluating 12 weeks of albiglutide in New York Heart Association II or III subjects with ejection fraction <40%. Subjects received weekly placebo (n = 30) or albiglutide 3...
July 2016: JACC. Heart Failure
Xia Guo, Qing Yang, Jianjun Dong, Lin Liao, Weiwei Zhang, Fupeng Liu
BACKGROUND AND OBJECTIVE: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a novel class of injectable antidiabetic drugs. Previous studies indicated that GLP-1RAs (exenatide and liraglutide) might increase the incidence of pancreatitis and pancreatic cancer. Here, we evaluated the clinical safety of once-weekly GLP-1RAs with respect to tumour risk. METHODS: Relevant studies were selected from Randomized controlled trials that reported the incidences of neoplasms were included in our research...
June 2016: Clinical Drug Investigation
Sheena Kayaniyil, Greta Lozano-Ortega, Heather A Bennett, Kristina Johnsson, Alka Shaunik, Susan Grandy, Bernt Kartman
INTRODUCTION: Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), approved for treatment of type 2 diabetes mellitus (T2DM). There is limited direct evidence comparing the efficacy and tolerability of exenatide 2 mg once weekly (QW) to other GLP-1 RAs. A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide QW versus other GLP-1 RAs for the treatment of adults with T2DM inadequately controlled on metformin monotherapy...
March 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
David Bruhn, Alan A Martin, Ruben Tavares, Barnaby Hunt, Richard F Pollock
Objective To compare the cost-utility of the glucagon-like peptide-1 receptor agonist albiglutide with those of insulin lispro (both in combination with insulin glargine), insulin glargine, and the dipeptidyl peptidase-4 inhibitor sitagliptin, representing treatments along the type 2 diabetes treatment continuum. Methods The Centre for Outcomes Research and Effectiveness (CORE) Diabetes Model was used for the cost-utility analysis. Data from three Phase 3 clinical trials (HARMONY 6, HARMONY 4, and HARMONY 3) evaluating albiglutide for the treatment of patients with type 2 diabetes were used for the baseline characteristics and treatment effects...
July 2016: Journal of Medical Economics
Baptist Gallwitz
This chapter deals with novel therapeutic approaches, predominantly for type 2 diabetes. Incretin-based therapies utilize the effects of glucagon-like peptide-1 (GLP-1), which stimulates insulin and inhibits glucagon secretion in a glucose-dependent manner. Incretin-based therapies comprise injectable GLP-1 receptor agonists and orally active dipeptidyl peptidase-IV inhibitors. Both have a low hypoglycaemia risk. GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, albiglutide) reduce glycated haemoglobin levels more effectively than oral antidiabetic agents do and lead to weight loss as well as a slight decrease in systolic blood pressure...
2016: Endocrine Development
Arun K Sharma, Punniyakoti V Thanikachalam, Satyendra K Rajput
Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects...
February 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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