Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: A double-blind, randomized, placebo-controlled study in healthy male volunteers

Bergman, Arthur; Stevens, C. Melinda; Zhou, Yanyan; Yi, Bingming; Laethem, Martine E.; Smet, M. De; Snyder, Karen; Hilliard, Deborah; Tanaka, Wesley; Zeng, Wei; Tanen, Michael; Wang, Amy Q.; Chen, Li; Winchell, Gregory A.; Davies, Michael J.; Ramael, Steven; Wagner, John A.; Herman, Gary

doi:10.1016/j.clinthera.2006.01.015

Cited by 249 publications

(253 citation statements)

References 33 publications

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“…On the other hand, a possible superiority of vildagliptin over other DPP-4 inhibitors regarding a hypoglycemic effect [11,12] was also reported. The IC 50 for vildagliptin and sitagliptin, the concentration required to achieve 50% inhibition of DPP-4 activity, is reportedly 5 nmol/L [13] and 26.3 nmol/L [14], respectively, which suggests that vildagliptin might be a potent DPP-4 inhibitor. Accordingly, a previous study showed that elevated levels of intact incretin hormones are maintained for a longer period following the administration of vildagliptin than that following the administration of sitagliptin [15].…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitor Switching as an Alternative Add-on Therapy to Current Strategies Recommended by Guidelines: Analysis of a Retrospective Cohort of Type 2 Diabetic Patients

Tanaka¹,

Nishimura²,

Sekioka³

et al. 2016

J Diabetes Metab

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Objective: This retrospective cohort study aimed to investigate the significance of dipeptidyl peptidase-4 (DPP-4) inhibitor switch therapy, which is currently not recommended by major diabetes guidelines. Methods:The subjects were 238 outpatients with type 2 diabetes who had been prescribed sitagliptin 50 mg daily, which was subsequently changed in one of three ways. Patients whose sitagliptin was switched to vildagliptin 50 mg twice daily were defined as the switched group. Patients whose sitagliptin was increased to 100 mg once daily were defined as the increased group. Patients who received an additional alfa-glucosidase inhibitor (α-GI) three times daily prior to meals and sitagliptin 50 mg once daily were defined as the added group. The primary endpoint was the glycated hemoglobin (HbA1c) value at 6 months after the medication change. Patients whose oral hypoglycemic agents were changed within 6 months after switching to vildagliptin, increasing sitagliptin, or adding α-GI were excluded from the full analysis set and the remaining patients were included in the per protocol analysis. Results:The per protocol analysis revealed that the HbA1c level decreased significantly in the switched group (n=71) and the added group (n=18) but did not change significantly in the increased group (n=69). Analysis of the full set showed that the HbA1c level decreased significantly in all three groups (switched [n=92], increased [n=88], and added [n=25]).

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Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibitor Switching as an Alternative Add-on Therapy to Current Strategies Recommended by Guidelines: Analysis of a Retrospective Cohort of Type 2 Diabetic Patients

Tanaka¹,

Nishimura²,

Sekioka³

et al. 2016

J Diabetes Metab

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“…Dipeptidyl peptidase-4 inhibitors exert their actions in part via augmentation of GLP-1 action, which leads to reduction of glucagon, increases in insulin and reduced glycaemia in human participants [28,29]. Moreover, GLP-1 administration reduced postprandial circulating lipid levels in human participants [18], although the underlying mechanisms remain uncertain.…”

Section: Discussionmentioning

confidence: 99%

The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice

et al. 2009

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Aims/hypothesis Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors attenuate postprandial lipaemia through mechanisms that remain unclear. As dyslipidaemia is a contributing risk factor for cardiovascular disease in type 2 diabetes, we examined the mechanisms linking pharmacological and physiological regulation of GLP-1 action to control of postprandial lipid metabolism.Methods Postprandial lipid synthesis and secretion were assessed in normal and fructose-fed hamsters and in wildtype mice that were treated with or without sitagliptin. Apolipoprotein B-48 (ApoB-48) synthesis and secretion were also examined in primary enterocyte cultures. The importance of exogenous vs endogenous GLP-1R signalling for regulation of intestinal lipoprotein synthesis and secretion was assessed in mice and hamsters treated with the GLP-1R agonist exendin-4, the GLP-1R antagonist exendin(9-39) and in Glp1r Electronic supplementary material The online version of this article

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“…Human data for vildagliptin (Ahren et al, 2005) has been submitted under New Drug Applications for review by the FDA. Sitagliptin (Bergman et al, 2006;Herman et al, 2005) was approved for marketing in October 2006. Saxagliptin (Augeri et al, 2005) and denagliptin are in phase III and phase II clinical trials respectively.…”

Section: Glp-1r Agonists and Dpp-1v Inhibitorsmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: A double-blind, randomized, placebo-controlled study in healthy male volunteers

Cited by 249 publications

References 33 publications

Dipeptidyl Peptidase-4 Inhibitor Switching as an Alternative Add-on Therapy to Current Strategies Recommended by Guidelines: Analysis of a Retrospective Cohort of Type 2 Diabetic Patients

Dipeptidyl Peptidase-4 Inhibitor Switching as an Alternative Add-on Therapy to Current Strategies Recommended by Guidelines: Analysis of a Retrospective Cohort of Type 2 Diabetic Patients

The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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