Dipeptidyl Peptidase-4 (DPP4) Inhibitors

2022 ◽  
pp. 583-599
Author(s):  
Ngoc-Yen T. Pham ◽  
Christos Argyropoulos ◽  
Nhan Dinh
Keyword(s):  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors

scholarly journals DIPEPTIDYL PEPTIDASE-4 INHIBITORS: POTENTIAL FOR TREATMENT OF METABOLIC SYNDROME AND DEVELOPED FORMULATION APPROACHES

2017 ◽  
Vol 10 (11) ◽  
pp. 20
Author(s):  
Rakesh Kumar Mishra ◽  
Shashikant Dhole
Keyword(s):  
Metabolic Syndrome ◽  
Cardiometabolic Risk ◽  
Immediate Release ◽  
Dipeptidyl Peptidase ◽  
Clinical Findings ◽  
Review Article ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Sustain Release ◽  
Dipeptidyl Peptidase 4 Inhibitors

  This review article deals with the pre-clinical and clinical findings reviewed or investigated by the researchers on dipeptidyl peptidase-4 (DPP4) inhibitors as a potential in the treatment of metabolic syndrome. Most of the researchers reported the activity of DPP4 inhibitors in the management of obesity, hyperlipidemia, hypertension, atherosclerosis, and in cardiometabolic risk which are summarized in the article. This article also focuses on the formulation approaches in which the formulators have reported and used in the designing or development of DPP4 inhibitors as dosage form. The formulation approaches which are commonly employed on DPP4 inhibitors are immediate release, sustain release, and combination therapy.  

Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes

2010 ◽  
Vol 20 (15) ◽  
pp. 4395-4398 ◽  
Author(s):  
Robert P. Brigance ◽  
Wei Meng ◽  
Aberra Fura ◽  
Thomas Harrity ◽  
Aiying Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors

Abstract 555: The Effect Of Dipeptidyl Peptidase 4 Inhibition On Arterial Blood Pressure Is Context Dependent

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Zaichuan Mi ◽  
Stevan P Tofovic ◽  
Delbert G Gillespie
Keyword(s):  
Blood Pressure ◽  
Dipeptidyl Peptidase ◽  
Sprague Dawley ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
The Metabolic Syndrome ◽  
Arterial Blood ◽  
Blood Pressures ◽  
Context Dependent ◽  
Wistar Kyoto

Dipeptidyl peptidase 4 (DPP4) inhibitors decrease the metabolism of endogenous glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, such as GLP-1(7-36)NH 2 , and GLP-1R agonists are antihypertensive. However, DPP4 inhibitors also impair the metabolism of endogenous Y 1 receptor (Y 1 R) agonists, such as neuropeptide Y 1-36 (NPY 1-36 ), and Y 1 R agonists are pro-hypertensive. Consequently, the long-term effect of DPP4 inhibition on blood pressure may be context dependent. To test this, we conducted radiotelemetry studies under highly controlled conditions to quantify the effects of chronic sitagliptin (80 mg/kg/day; DPP4 inhibitor) on blood pressure in spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and Zucker Diabetic-Sprague Dawley rats (ZDSD; model of the metabolic syndrome developed by PreClinOmics). In SHR, chronic (3 weeks) administration of sitagliptin significantly increased systolic, mean and diastolic blood pressures by 10.3, 9.2 and 7.9 mmHg, respectively (p<0.01). Sitagliptin also significantly (p<0.01) increased blood pressure in SHR treated with hydralazine (vasodilator; 25 mg/kg/day) or enalapril (ACE inhibitor; 10 mg/kg/day). Co-administration of BIBP3226 (2 mg/kg/day; Y 1 R antagonist) abolished the pro-hypertensive effects of sitagliptin in SHR. In WKY, chronic sitagliptin slightly decreased (p<0.01) systolic, mean and diastolic blood pressures (-1.8, -1.1 and -0.4 mmHg, respectively). In ZDSD, chronic sitagliptin markedly decreased systolic, mean and diastolic blood pressures (-7.7, -5.8, -4.3 mmHg, respectively). In isolated, perfused ZDSD kidneys pretreated with norepinephrine to induce basal tone, NPY 1-36 and GLP-1(7-36)NH 2 exerted little effect on renovascular tone. In contrast, in isolated SHR kidneys, both NPY 1-36 and GLP-1(7-36)NH 2 elicited potent and efficacious vasoconstriction (increased perfusion pressure by 171 and 132 mmHg, respectively). Conclusions: 1) The effects of DPP4 inhibitors on blood pressure are context dependent; 2) The context-dependent effects of DPP4 inhibitors are due in part to differential renovascular responses to its most important substrates (NPY 1-36 and GLP-1(7-36)NH 2 ); 3) Y 1 R antagonists may augment the beneficial effects of DPP4 inhibitors.

Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors

2016 ◽  
Vol 24 (21) ◽  
pp. 5534-5545 ◽  
Author(s):  
Dmitri A. Pissarnitski ◽  
Zhiqiang Zhao ◽  
David Cole ◽  
Wen-Lian Wu ◽  
Martin Domalski ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Scaffold Hopping ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors

scholarly journals Oxytocin May be Superior to Gliptins as a Potential Treatment for Diabetic COVID-19 Patients

2021 ◽  
Vol 2 ◽  
pp. 106-107
Author(s):  
Phuoc-Tan Diep
Keyword(s):  
Type 2 Diabetes ◽  
Full Text ◽  
Dipeptidyl Peptidase ◽  
Potential Treatment ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Dpp4 Inhibitor ◽  
Increased Risk ◽  
Immunomodulatory Properties

Diabetes is a comorbidity associated with an increased risk of severe COVID-19. Gliptins are anti-diabetic drugs that inhibit dipeptidyl peptidase-4 (DPP4) and they have been proposed as a possible treatment for COVID-19 patients with and without diabetes due to their immunomodulatory properties. Oxytocin has also been proposed as a treatment for COVID-19 due to its immunomodulatory properties as well as other mechanisms. In addition, oxytocin has been identified as a natural DPP4 inhibitor. Therefore, oxytocin not only has the properties associated with DPP4 inhibition but it has numerous additional beneficial properties. It is proposed that oxytocin may be superior to DPP4 inhibitors for COVID-19 patients especially for patients with type 2 diabetes. Doi: 10.28991/SciMedJ-2020-02-SI-10 Full Text: PDF

Abstract 95: Glucagon Like Peptide-1 (GLP-1) Does Not Cause Vasodilation Even When Dipeptidyl Peptidase 4 (DPP4) is Inhibited

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jessica K Devin ◽  
Mias Pretorius ◽  
Frederic T Billings ◽  
Hui Nian ◽  
Nancy J Brown
Keyword(s):  
Interactive Effect ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Baseline Heart Rate ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dpp4 Inhibition

Glucagon-like peptide 1 (GLP-1) causes direct vasodilation in animal models. Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in diabetic patients by preventing the degradation of GLP-1. The direct effect of GLP-1 in the human vasculature, and how it is altered by DPP4 inhibition, has not been reported. This study tested the hypothesis that intra-arterial infusion of GLP-1 causes dose-dependent vasodilation, and that DPP4 inhibition potentiates the forearm blood flow (FBF) response to GLP-1 by decreasing its degradation. Eight healthy, non-obese (BMI<30 kg/m 2 ) subjects, age 28-54 years old (3 female) participated in this double-blind, placebo-controlled crossover study. On study days separated by at least one week subjects received DPP4 inhibitor (sitagliptin 200 mg p.o.) or placebo, followed by infusion of GLP-1 in the brachial artery at graded doses (0.45-3.60 pmol/min) for 5 minutes per dose. Sitagliptin significantly decreased plasma DPP4 activity (p<0.001 vs. placebo). Sitagliptin did not significantly affect baseline heart rate or baseline FBF. Baseline mean arterial pressure was significantly higher during sitagliptin than during placebo [87.13 ± 2.10 mmHg versus 84.75 ± 3.28 mmHg, p=0.037]. GLP-1 concentrations were significantly higher after sitagliptin (Left Figure; N=5). There was no effect of GLP-1 on FBF either in the presence or absence of sitagliptin. Moreover, there was no interactive effect of GLP-1 and sitagliptin on FBF (Right Figure). GLP-1 does not cause vasodilation in healthy humans even when its degradation is inhibited. These data have implications for the cardiovascular effects of DPP4 inhibitors and GLP-1 receptor agonists.

Abstract 503: Dipeptidyl Peptidase-4 Regulates Proliferation of and Collagen Synthesis by Cardiac Fibroblasts

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Delbert G Gillespie
Keyword(s):  
Collagen Synthesis ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Dipeptidyl Peptidase ◽  
Cell Number ◽  
Biologically Active ◽  
P Value ◽  
Collagen Production ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors

Dipeptidyl peptidase-4 (DPP4) inhibitors, for example sitagliptin, are a new class of drugs for treatment of type 2 diabetes. Because there are multiple peptide substrates for DPP4, inhibition of DPP4 may entail risks due to augmented levels of biologically active peptides. The purpose of this study was to investigate the role of DPP4 in regulating the effects of two of its substrates, neuropeptide Y 1-36 (NPY 1-36 ) and peptide YY 1-36 (PYY 1-36 ) (naturally occurring Y 1 receptor agonists) on proliferation of and collagen production by cardiac fibroblasts (CFs) from spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats. For proliferation experiments, subconfluent cells were treated every 24 hours for 4 days with platelet-derived growth factor-BB (PDGF) and various treatments, and cells were dislodged and counted. For collagen synthesis experiments, confluent cells were treated with PDGF, tritiated-L-proline and various treatments, and after 48 hours radioactivity in cells was quantified. In both SHR and WKY CFs, both NPY 1-36 and PYY 1-36 (1 to 10 nmol/L) increased cell number and proline incorporation (index of collagen synthesis). Sitagliptin (1 μmol/L) significantly enhanced these effects. For example, in SHR CFs 10 nmol/L of NPY 1-36 increased cell number from 37,588 ± 503 to 51,990 ± 649; yet in the presence of sitagliptin, NPY 1-36 increased cell number from 37,964 ± 508 to 62,047 ± 939 (mean ± SEM, n=6; p<0.000001, p-value for interaction between sitagliptin and NPY 1-36 ). In both SHR and WKY CFs and in both the absence and presence of sitagliptin, BIBP3226 (1 μmol/L; Y 1 receptor antagonist) blocked all effects of NPY 1-36 and PYY 1-36 . Because DPP4 metabolizes NPY 1-36 to NPY 3-36 and PYY 1-36 to PYY 3-36 , we also determined the effects of NPY 3-36 and PYY 3-36 on proliferation and collagen production. In both SHR and WKY CFs, these metabolites did not affect proliferation or collagen production, either in the absence or presence of sitagliptin. Conclusion: In cultured CFs, DPP4 inhibitors increase NPY 1-36 and PYY 1-36 induced activation of Y 1 receptors leading to increased proliferation and collagen production. Therefore, DPP4 inhibitors might increase cardiac fibrosis in patients with chronically elevated levels of NPY 1-36 or PYY 1-36 .

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