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Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus

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17 papers 25 to 100 followers
By Ehud Ur Professor and Head, Endocrinology, UBC, Vancouver
Steven P Marso, Stephen C Bain, Agostino Consoli, Freddy G Eliaschewitz, Esteban Jódar, Lawrence A Leiter, Ildiko Lingvay, Julio Rosenstock, Jochen Seufert, Mark L Warren, Vincent Woo, Oluf Hansen, Anders G Holst, Jonas Pettersson, Tina Vilsbøll
Background Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. Methods We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks...
September 15, 2016: New England Journal of Medicine
Thomas Fremming Dejgaard, Christian Seerup Frandsen, Tanja Stenbæk Hansen, Thomas Almdal, Søren Urhammer, Ulrik Pedersen-Bjergaard, Tonny Jensen, Andreas Kryger Jensen, Jens Juul Holst, Lise Tarnow, Filip Krag Knop, Sten Madsbad, Henrik Ullits Andersen
BACKGROUND: The combination of insulin and glucagon-like peptide-1 (GLP-1) receptor agonist therapy improves glycaemic control, induces weight loss, and reduces insulin dose needed in type 2 diabetes. We assessed the efficacy and safety of the GLP-1 receptor agonist liraglutide as an add-on therapy to insulin for overweight adult patients with type 1 diabetes. METHODS: We did a randomised, double-blind, placebo-controlled trial at Steno Diabetes Center (Gentofte, Denmark)...
March 2016: Lancet Diabetes & Endocrinology
Darleen Sandoval, Stephanie R Sisley
Type 2 diabetes is often treated with a class of drugs referred to as glucagon-like peptide-1 (GLP-1) analogs. GLP-1 is a peptide secreted by the gut that acts through only one known receptor, the GLP-1 receptor. The primary function of GLP-1 is thought to be lowering of postprandial glucose levels. Indeed, medications utilizing this system, including the long-acting GLP-1 analogs liraglutide and exenatide, are beneficial in reducing both blood sugars and body weight. GLP-1 analogs were long presumed to affect glucose control through their ability to increase insulin levels through peripheral action on beta cells...
December 15, 2015: Molecular and Cellular Endocrinology
Caroline Bonner, Julie Kerr-Conte, Valéry Gmyr, Gurvan Queniat, Ericka Moerman, Julien Thévenet, Cédric Beaucamps, Nathalie Delalleau, Iuliana Popescu, Willy J Malaisse, Abdullah Sener, Benoit Deprez, Amar Abderrahmani, Bart Staels, François Pattou
Type 2 diabetes (T2D) is characterized by chronic hyperglycemia resulting from a deficiency in insulin signaling, because of insulin resistance and/or defects in insulin secretion; it is also associated with increases in glucagon and endogenous glucose production (EGP). Gliflozins, including dapagliflozin, are a new class of approved oral antidiabetic agents that specifically inhibit sodium-glucose co-transporter 2 (SGLT2) function in the kidney, thus preventing renal glucose reabsorption and increasing glycosuria in diabetic individuals while reducing hyperglycemia...
May 2015: Nature Medicine
Oriana Hoi Yun Yu, Kristian B Filion, Laurent Azoulay, Valerie Patenaude, Agnieszka Majdan, Samy Suissa
OBJECTIVE: To determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF...
February 2015: Diabetes Care
Kathleen M Dungan, Santiago Tofé Povedano, Thomas Forst, José G González González, Charles Atisso, Whitney Sealls, Jessie L Fahrbach
BACKGROUND: Dulaglutide and liraglutide, both glucagon-like peptide-1 (GLP-1) receptor agonists, improve glycaemic control and reduce weight in patients with type 2 diabetes. In a head-to-head trial, we compared the safety and efficacy of once-weekly dulaglutide with that of once-daily liraglutide in metformin-treated patients with uncontrolled type 2 diabetes. METHODS: We did a phase 3, randomised, open-label, parallel-group study at 62 sites in nine countries between June 20, 2012, and Nov 25, 2013...
October 11, 2014: Lancet
Michael Nauck, Ruth S Weinstock, Guillermo E Umpierrez, Bruno Guerci, Zachary Skrivanek, Zvonko Milicevic
OBJECTIVE: To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks. RESEARCH DESIGN AND METHODS: This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8...
August 2014: Diabetes Care
Michaela Diamant, Michael A Nauck, Rimma Shaginian, James K Malone, Simon Cleall, Matthew Reaney, Danielle de Vries, Byron J Hoogwerf, Leigh MacConell, Bruce H R Wolffenbuttel
OBJECTIVE: Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. RESEARCH DESIGN AND METHODS: In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5...
October 2014: Diabetes Care
Conrad Eng, Caroline K Kramer, Bernard Zinman, Ravi Retnakaran
BACKGROUND: Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide robust glucose-lowering capability with low risk of hypoglycaemia or weight gain. We thus did a systematic review and meta-analysis of randomised controlled trials to assess the effect of this combination treatment on glycaemic control, hypoglycaemia, and weight gain in patients with type 2 diabetes. METHODS: We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA...
December 20, 2014: Lancet
Laura A Young, John B Buse
No abstract text is available yet for this article.
December 20, 2014: Lancet
Laurie L Baggio, Daniel J Drucker
The peptide hormone glucagon-like peptide-1 (GLP-1) enhances glucose-induced insulin secretion and inhibits both gastric emptying and glucagon secretion. GLP-1 receptor (GLP-1R) agonists control glycemia via glucose-dependent mechanisms of action and promote weight loss in obese and diabetic individuals. Nevertheless, the mechanisms and cellular targets transducing the weight loss effects remain unclear. Two recent studies in the JCI provide insight into the neurons responsible for this effect. Sisley et al...
October 2014: Journal of Clinical Investigation
Anna Secher, Jacob Jelsing, Arian F Baquero, Jacob Hecksher-Sørensen, Michael A Cowley, Louise S Dalbøge, Gitte Hansen, Kevin L Grove, Charles Pyke, Kirsten Raun, Lauge Schäffer, Mads Tang-Christensen, Saurabh Verma, Brent M Witgen, Niels Vrang, Lotte Bjerre Knudsen
Liraglutide is a glucagon-like peptide-1 (GLP-1) analog marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide also reduces body weight. It is not fully understood how liraglutide induces weight loss or to what degree liraglutide acts directly in the brain. Here, we determined that liraglutide does not activate GLP-1-producing neurons in the hindbrain, and liraglutide-dependent body weight reduction in rats was independent of GLP-1 receptors (GLP-1Rs) in the vagus nerve, area postrema, and paraventricular nucleus...
October 2014: Journal of Clinical Investigation
Jean-Luc Faillie, Laurent Azoulay, Valerie Patenaude, Dominique Hillaire-Buys, Samy Suissa
OBJECTIVES: To determine whether the use of incretin based drugs, compared with sulfonylureas, is associated with an increased risk of acute pancreatitis. DESIGN: Population based cohort study. SETTING: 680 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink. PARTICIPANTS: From 1 January 2007 to 31 March 2012, 20 748 new users of incretin based drugs were compared with 51 712 users of sulfonylureas and followed up until 31 March 2013...
2014: BMJ: British Medical Journal
Ling Li, Jiantong Shen, Malgorzata M Bala, Jason W Busse, Shanil Ebrahim, Per Olav Vandvik, Lorena P Rios, German Malaga, Evelyn Wong, Zahra Sohani, Gordon H Guyatt, Xin Sun
OBJECTIVE: To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ELIGIBILITY CRITERIA: Randomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs...
2014: BMJ: British Medical Journal
Emily Kern, Lisa B VanWagner, Guang-Yu Yang, Mary E Rinella
IMPORTANCE: Use of incretin-based hypoglycemic agents is increasing, but safety data remain limited. We treated a woman with marker-negative autoimmune hepatitis associated with the glucagon-like peptide 1 agonist liraglutide. OBSERVATIONS: A young woman with type 2 diabetes mellitus and vitiligo presented with a 10-day history of acute hepatitis. Other than starting liraglutide therapy 4 months prior, she reported no changes in medication therapy and no use of supplements...
June 2014: JAMA Internal Medicine
Stephanie Sisley, Ruth Gutierrez-Aguilar, Michael Scott, David A D'Alessio, Darleen A Sandoval, Randy J Seeley
Glucose control and weight loss are cornerstones of type 2 diabetes treatment. Currently, only glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance. Both glucose and body weight are regulated by the brain, which contains GLP1 receptors (GLP1R). Even though the brain is poised to mediate the effects of GLP1 analogs, it remains unclear whether the glucose- and body weight-lowering effects of long-acting GLP1R agonists are via direct action on CNS GLP1R or the result of downstream activation of afferent neuronal GLP1R...
June 2014: Journal of Clinical Investigation
Megan J Dailey, Timothy H Moran
Glucagon-like peptide 1 (GLP-1) and GLP-1 analogs have received much recent attention due to the success of GLP-1 mimetics in treating type II diabetes mellitus (T2DM), but these compounds may also have the potential to treat obesity. The satiety effect of GLP-1 may involve both within-meal enteroenteric reflexes, and across-meal central signaling mechanisms, that mediate changes in appetite and promote satiety. Here, we review data supporting the role of both peripheral and central GLP-1 signaling in the control of gastrointestinal motility and food intake...
February 2013: Trends in Endocrinology and Metabolism: TEM
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