Sitagliptin

Drucker, Daniel J.; Easley, Chris; Kirkpatrick, Peter

doi:10.1038/nrd2245

Cited by 65 publications

(49 citation statements)

References 10 publications

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“…On the other hand, sitagliptin inhibited the activity of DPP-4 and potentiates the action of incretins (GLP-1 and GIP). GLP-1 has anti-inflammatory, anti-atherogenic property and potential for treatment of cardiovascular diseases [11][12][13][14][15]. Thus, due to significant anti-platelet activity and inhibitory actions on DPP-4 of sitagliptin, it can be useful for diseases like T2DM.…”

Section: Discussionmentioning

confidence: 99%

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Sitagliptin: Anti-platelet effect in diabetes and healthy volunteers

et al. 2012

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Sitagliptin, a selective dipeptidyl peptidase-4 inhibitor drug is used to treat type-2 diabetes (T2DM). We investigated the anti-platelet activity of sitagliptin in patients with T2DM and in in vitro samples obtained from healthy humans. Patients with T2DM (27 male + 23 female) were selected and followed up before (control) and after treatment with sitagliptin for up to 3 months. Platelets were isolated from the blood of sitagliptin treated patients and controls. Patients with T2DM treated with sitagliptin for 1and 3 months, showed 10 ± 2% and 30 ± 5% inhibition of platelet aggregation, respectively. For the in vitro study, platelets from 10 normal humans (n = 10) were isolated. Platelet aggregation, intracellular free calcium and tyrosine phosphorylation of multiple proteins were measured by aggregometer, spectrofluorometer and western blotting, respectively. Platelets pre-treated with 5 and 10 µg/ml of sitagliptin, showed 25 ± 4% and 40 ± 6% inhibition of thrombin-induced platelet aggregation, respectively. Sitagliptin decreased intracellular free calcium (2.5-fold) and tyrosine phosphorylation of multiple proteins in thrombin-induced platelet activation. Sitagliptin inhibited platelet aggregation in T2DM as well as in healthy humans. Sitagliptin has significant concentration-dependent anti-platelet activity. This activity was due to its inhibitory effect on intracellular free calcium and tyrosine phosphorylation.

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Section: Discussionmentioning

confidence: 99%

“…In patients with T2DM, incretins effects were found to be significantly impaired [11]. Sitagliptin inhibits the proteolytic activity of dipeptidyl peptidase-4 (DPP-4), thereby potentiating the action of incretins such as glucagon-like peptide (GLP)-1 and glucosedependent insulinotropic polypeptide (GIP) [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Sitagliptin: Anti-platelet effect in diabetes and healthy volunteers

et al. 2012

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“…In the two months prior to writing this article the following were offered in published patent applications: glucagon-like peptide-1 and -2 analogues, dipeptidyl peptidase IV inhibitors, glucokinase stimulators, diacylglycerol acyltransferase inhibitors, 11β-hydroxysteroid dehydrogenase inhibitors and α-melanocortin stimulating hormone agonists. Of these, a dipeptidyl peptidase IV inhibitor has recently been approved by the FDA in the US [41]. As expected, the range of targets is substantial.…”

Section: Targeting Biological Mechanisms In the Metabolic Syndromementioning

confidence: 97%

Drug discovery in the metabolic syndrome: context and some recent developments

Suckling¹

2007

Expert Opinion on Therapeutic Targets

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The metabolic syndrome, encompassing the clinically distinct but related areas of dyslipidaemia, insulin resistance, obesity and vascular disease, offers a wide arena for drug discovery. There is substantial and growing unmet medical need, particularly as the worldwide epidemic of obesity continues to develop. There are also many targets and biological mechanisms that can be exploited. However, the context for clinical development is challenging because of the many ways in which the syndrome can be approached. As with most therapeutic areas, preclinical data provide only limited confidence in the potential of a novel target in humans. In this review, the author outlines the context for drug discovery in the metabolic syndrome, the clinical and biological scope and recent developments in preclinical models. Finally, existing examples of drug targets for a range of biological mechanisms are considered, outlining their biology and points relevant to lead identification and optimisation and clinical development.

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“…12 Sitagliptin is an oral medication and is the first drug on the market in the dipeptidyl peptidase-4 (DPP-4) inhibitor class. 13 DPP-4 inhibitors prevent the actions of the endogenous enzyme DPP-4, which breaks down the body's own incretins. 14 As such, sitagliptin enhances glucose-induced insulin secretion and inhibits glucagon release, although it has been shown to have no effect on gastric emptying.…”

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confidence: 99%