Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus

Kolterman, Orville G.; Kim, Dennis Dong Hwan; Shen, Larry Z.; Ruggles, James A.; Nielsen, Loretta L.; Fineman, Mark; Baron, Alain

doi:10.1093/ajhp/62.2.173

Cited by 374 publications

(241 citation statements)

References 34 publications

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“…Yet, the hormone GLP-1 retains its insulinotropic effect, at least in supraphysiological concentrations [2]. For this reason, GLP-1 receptor agonists like exenatide are clinically beneficial in diabetic people [3,5,7]. In this study, we examined the effect of a longacting formulation of exenatide, exenatide ER, over the course of 12 wk in healthy cats.…”

Section: Discussionmentioning

confidence: 99%

“…As a result of the numerous beneficial effects in the diabetic state, incretin-based drugs have been developed and are commercially available for adjunctive treatment of type II DM in people [3][4][5][6][7][8]. Exenatide has been shown to be as effective as insulin glargine in the treatment of human type II DM but with fewer side effects such as weight gain and hypoglycemia [3].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Rudinsky

Adin

Borin-Crivellenti

et al. 2015

Domestic Animal Endocrinology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Rudinsky

Adin

Borin-Crivellenti

et al. 2015

Domestic Animal Endocrinology

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“…However, GLP-1 use as a therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM) is impractical because of its extremely short half-life (1.5 min in rodents and humans) [7]. Exendin-4 is a more stable GLP-1 analog, with a half-life of approximately 4 h in humans [8]. Its synthetic form (i.e., exenatide) was approved by the US Food and Drug Administration in April 2005 as an adjunctive therapy to metformin, a sulfonylurea or a thiazolidinedione for the treatment of T2DM.…”

Section: Introductionmentioning

confidence: 99%

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Luciani

Deledda

Benvenuti

et al. 2010

Cell. Mol. Life Sci.

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Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na(+) channels and amplitude of Ca(++) currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases.

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“…Exendin-4 is a potent GLP-1 receptor agonist and mimics the effects of GLP-1 completely [39]. Because exenatide is not metabolized by DPP-IV it has an extended half-life relative to native GLP-1 (4 hours in humans following subcutaneous injection) [40], and also an extended period of pharmacologic activity. When administered intravenously to healthy humans, exenatide caused a small decrease in fasting glucose with a minimal effect on fasting insulin levels [41].…”

Section: Glp-1 Mimeticsmentioning

confidence: 99%

Utilizing the GLP-1 signaling system to treat diabetes: Sorting through the pharmacologic approaches

D’Alessio

Vahl

2005

Curr Diab Rep

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Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that promotes glucose homeostasis through the regulation of insulin and glucagon secretion, gastric emptying, and food intake. This spectrum of effects makes GLP-1 an attractive candidate for drug development. However, because GLP-1 is a small peptide with rapid metabolism in the circulation, its usefulness to treat patients is limited. However, GLP-1 mimetics that are resistant to degradation have been developed and are effective in lowering blood glucose in diabetic patients. A second strategy for harnessing GLP-1 therapeutically is to inhibit the metabolism of endogenous GLP-1; several orally available compounds are in clinical trials. These two new classes of drugs both enhance GLP-1 signaling but differ in several key characteristics that may lead to distinct roles in the treatment of diabetic patients.

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Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus

Cited by 374 publications

References 34 publications

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Utilizing the GLP-1 signaling system to treat diabetes: Sorting through the pharmacologic approaches

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