Literature DB >> 12843147

Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes.

Orville G Kolterman1, John B Buse, Mark S Fineman, Eling Gaines, Sonja Heintz, Thomas A Bicsak, Kristin Taylor, Dennis Kim, Maria Aisporna, Yan Wang, Alain D Baron.   

Abstract

Despite the advent of new treatments, glucose control in the type 2 diabetes population is unsatisfactory. AC2993 (synthetic exendin-4; exenatide), a novel glucose-dependent insulinotropic agent, exhibited notable antidiabetic potential in two clinical studies in patients with type 2 diabetes. In study A, 24 subjects received sc injections of study medication (0.1 micro g/kg AC2993 or placebo) twice daily with meals for 5 d. Statistically significant reductions in mean postprandial circulating concentrations of glucose, insulin, and glucagon occurred following treatment with AC2993. In study B, 13 subjects receiving a single dose of study medication (0.05, 0.1, or 0.2 micro g/kg AC2993 or placebo) following an overnight fast had reduced fasting plasma glucose concentrations during the subsequent 8-h period. The relative glucose and insulin concentration profiles were consistent with glucose-dependent insulinotropism. AC2993 was well tolerated. Mild transient headache, nausea, and vomiting were the main adverse events. In conclusion, AC2993 acutely and markedly reduces fasting and postprandial glucose concentrations in patients with type 2 diabetes. During fasting, glucose-dependent enhancement of insulin secretion and suppression of glucagon secretion are the predominant mechanisms, and postprandially, slowing of gastric emptying is additionally operative. This robust antidiabetic effect warrants further evaluation of AC2993.

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Year:  2003        PMID: 12843147     DOI: 10.1210/jc.2002-021545

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


  132 in total

1.  Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents.

Authors:  Krystyna Tatarkiewicz; Pamela A Smith; Emmanuel J Sablan; Clara J Polizzi; Donald E Aumann; Christiane Villescaz; Diane M Hargrove; Bronislava R Gedulin; Melissa G W Lu; Lisa Adams; Tina Whisenant; Denis Roy; David G Parkes
Journal:  Am J Physiol Endocrinol Metab       Date:  2010-10-05       Impact factor: 4.310

2.  Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.

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Journal:  J Gene Med       Date:  2010-06       Impact factor: 4.565

Review 3.  Glycemic control and weight reduction without causing hypoglycemia: the case for continued safe aggressive care of patients with type 2 diabetes mellitus and avoidance of therapeutic inertia.

Authors:  Stanley S Schwartz; Benjamin A Kohl
Journal:  Mayo Clin Proc       Date:  2010-11-24       Impact factor: 7.616

Review 4.  Glucagon-like peptide 1 (GLP-1).

Authors:  T D Müller; B Finan; S R Bloom; D D'Alessio; D J Drucker; P R Flatt; A Fritsche; F Gribble; H J Grill; J F Habener; J J Holst; W Langhans; J J Meier; M A Nauck; D Perez-Tilve; A Pocai; F Reimann; D A Sandoval; T W Schwartz; R J Seeley; K Stemmer; M Tang-Christensen; S C Woods; R D DiMarchi; M H Tschöp
Journal:  Mol Metab       Date:  2019-09-30       Impact factor: 7.422

Review 5.  Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

Authors:  Charlotte C Ronveaux; Daniel Tomé; Helen E Raybould
Journal:  J Nutr       Date:  2015-02-04       Impact factor: 4.798

6.  The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1.

Authors:  M A Nauck; A El-Ouaghlidi
Journal:  Diabetologia       Date:  2005-03-11       Impact factor: 10.122

Review 7.  Exenatide twice daily: a review of its use in the management of patients with type 2 diabetes mellitus.

Authors:  Paul L McCormack
Journal:  Drugs       Date:  2014-03       Impact factor: 9.546

8.  In vivo biological activity of exendin (1-30).

Authors:  Máire E Doyle; Patrick McConville; Michael J Theodorakis; Margaret M Goetschkes; Michel Bernier; Richard G S Spencer; Harold W Holloway; Nigel H Greig; Josephine M Egan
Journal:  Endocrine       Date:  2005-06       Impact factor: 3.633

9.  Exenatide.

Authors:  Gillian M Keating
Journal:  Drugs       Date:  2005       Impact factor: 9.546

Review 10.  Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus.

Authors:  Baptist Gallwitz
Journal:  Drug Saf       Date:  2010-02-01       Impact factor: 5.606

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