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Dpp 4 inhibitors

Bassam M Ayoub, Shereen Mowaka, Marwa M Safar, Nermeen Ashoush, Mona G Arafa, Haidy E Michel, Mariam M Tadros, Mohamed M Elmazar, Shaker A Mousa
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work...
June 12, 2018: Scientific Reports
Bradley S Fleenor, An Ouyang, T Dylan Olver, Jessica A Hiemstra, Melissa S Cobb, Gianmaria Minervini, Craig A Emter
Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine...
June 11, 2018: Hypertension
Poonam Kalhotra, Veera C S R Chittepu, Guillermo Osorio-Revilla, Tzayhri Gallardo-Velázquez
Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer...
June 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Weijia Xie, Xiaoxiao Song, Zhenjie Liu
Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications...
June 4, 2018: Vascular Pharmacology
Ankit Rohilla, Tanya Gupta, Ankita Pathak, Md J Akhtar, Md R Haider, Kashif Haider, Mohammad Shahar Yar
Diabetes has turned out to be an epidemic in the recent years all over the world, and today it has become a burden on the healthcare system. Over the years, with technological advancements, different classes of antidiabetic medications have emerged, like sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones, but these are often loaded with serious aftermaths like hypoglycemia, weight gain, cardiovascular and renal issues. Dipeptidyl peptidase-4 (DPP-4) inhibition is an exciting and new approach in the treatment of type-2 diabetes...
June 7, 2018: Archiv der Pharmazie
Helena W Rodbard
GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time...
June 5, 2018: Diabetes Technology & Therapeutics
Qi Li, Jiade Li, Yanli Liu, Mingyu Zhang, Chang Chen
Dipeptidyl peptidase IV (DPP-IV) inhibitors are novel oral anti-hyperglycemic agents. Here, the anti-apoptotic effect of Anagliptin in human umbilical vein endothelial cells (HUVECs) was evaluated. Cultured HUVECs were pre-incubated with Anagliptin, and then treated hydrongen peroxide (H2 O2 ) to induce apoptosis. The apoptosis of HUVECs were detected by viability, LIVE/DEAD staining assay and flow cytometry assays. HUVECs were transfected with plasmid harboring human NADPH oxidases (NOX) 4 or an empty vector...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Eugene A Zubkov, Yana A Zorkina, Elena V Orshanskaya, Nadezhda N Khlebnikova, Natalia A Krupina, Vladimir P Chekhonin
BACKGROUND: Previous studies have shown the development of emotional and motivational disorders, such as anxiety-depression-like disorders with increased aggression in adolescent and adult Wistar rats, occurs after neonatal exposure to the dipeptidyl peptidase-IV (DPP-IV, EC inhibitors diprotin A and sitagliptin (postnatal days 5-18). METHODS: In this study, using real-time PCR, we evaluated changes in the gene expression of serine protease DPP-IV and prolyl endopeptidase (PREP, EC 3...
June 1, 2018: Neuropsychobiology
Gian Paolo Fadini, Daniele Bottigliengo, Federica D'Angelo, Franco Cavalot, Antonio Carlo Bossi, Giancarlo Zatti, Ileana Baldi, Angelo Avogaro
INTRODUCTION: DPP-4 inhibitors (DPP4i) and sulfonylureas are popular second-line therapies for type 2 diabetes (T2D), but there is a paucity of real-world studies comparing their effectiveness in routine clinical practice. METHODS: This was a multicenter retrospective study on diabetes outpatient clinics comparing the effectiveness of DPP4i versus gliclazide extended release. The primary endpoint was change from baseline in HbA1c. Secondary endpoints were changes in fasting plasma glucose, body weight, and systolic blood pressure...
June 1, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Panagiotis Anagnostis, Pavlos Siolos, Konstantinos Christou, Nifon K Gkekas, Nikoletta Kosmidou, Vasilios G Athyros, Asterios Karagiannis
Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results...
March 2018: Hormones: International Journal of Endocrinology and Metabolism
Juan Ling, Long Ge, Ding-Hua Zhang, Yong-Feng Wang, Zhuo-Lin Xie, Jin-Hui Tian, Xiao-Hui Xiao, Ke-Hu Yang
AIMS: To evaluate the methodological quality of systematic reviews (SRs), and summarize evidence of important outcomes from dipeptidyl peptidase-4 inhibitors (DPP4-I) in treating type 2 diabetes mellitus (T2DM). METHODS: We included SRs of DPP4-I for the treatment of T2DM until January, 2018 by searching the Cochrane Library, PubMed, EMBASE and three Chinese databases. We evaluated the methodological qualities with the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool and the GRADE (The Grading of Recommendations Assessment, Development and Evaluation) approach...
June 1, 2018: Acta Diabetologica
Bruce C Stuart, Julia F Slejko, Juan-David Rueda, Catherine Cooke, Xian Shen, Pamela Roberto, Michael Ciarametaro, Robert Dubois
OBJECTIVES: To explore formulary restrictions on noninsulin antihyperglycemic drugs (NIADs) in Medicare Part D plans and to estimate the impact of formulary restrictions on use of NIADs among low-income subsidy (LIS) recipient enrollees with type 2 diabetes (T2D) undergoing treatment intensification. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort of 2919 LIS enrollees with T2D receiving metformin monotherapy during the first quarter of 2012 who intensified treatment later in the year was tracked to assess selection of and days' supply with sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and other NIADs...
May 2018: American Journal of Managed Care
Takuya Imatoh, Takumi Nishi, Midori Yasui, Toshiki Maeda, Kimie Sai, Yoshiro Saito, Hiroshi Une, Akira Babazono
PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients. METHODS: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016...
May 30, 2018: Pharmacoepidemiology and Drug Safety
Young-Gun Kim, Seirhan Kim, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Hae Jin Kim
Background: Information on the risk of acute pancreatitis in patients receiving dipeptidyl-peptidase IV inhibitors (DPP-4i) is limited and controversial. One study suggested that the differences in findings between these meta-analyses were attributed to whether they included large randomized control trials with cardiovascular outcomes or not. The aim of our study was to determine whether the use of DPP-4i increases the risk of acute pancreatitis compared with sulfonylurea (SU) and whether the risk is higher in patients with underlying cardiovascular disease (CVD)...
2018: Journal of Diabetes Research
Petr Jarolim, William B White, Christopher P Cannon, Qi Gao, David A Morrow
OBJECTIVE: Patients with type 2 diabetes are at increased risk of developing heart failure (HF). Enhanced recognition of patients at risk for HF would help guide therapeutic decisions. RESEARCH DESIGN AND METHODS: We investigated the prognostic implications of changes in N-terminal B-type natriuretic peptide (NT-proBNP) concentration in patients with type 2 diabetes and ischemic heart disease who were enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial, a phase 3b trial of alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor...
May 30, 2018: Diabetes Care
W Ryan Powell, Cindy L Christiansen, Donald R Miller
INTRODUCTION: Among the most pressing clinical decisions in type 2 diabetes treatments are which drugs should be used after metformin is no longer sufficient, and whether sulfonylureas (SUs) should remain as a suitable second-line treatment. In this article we summarize current evidence on the long-term safety risks associated with SU therapy relative to other oral glucose-lowering therapies. METHODS: The MEDLINE database and were searched for observational and experimental studies comparing the safety of SUs to that of other diabetes medications in people with type 2 diabetes mellitus through December 15, 2015...
May 28, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Ulf Elbelt
Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated...
June 2018: Deutsche Medizinische Wochenschrift
Yunyi Gao, Yujie Liang, Xingwu Ran
Objective: To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. Methods: The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. Results: DPP-4 inhibitors can accelerated the ulcer healing...
May 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
Katarina Tomovic, Jelena Lazarevic, Gordana Kocic, Marina Deljanin-Ilic, Marko Anderluh, Andrija Smelcerovic
Dipeptidyl peptidase-4 (DPP-4) cleaves N-terminal dipeptides, with Pro, Ala or Ser at the penultimate position, and, in that way, modulates biological activity of certain polypeptides. Due to its ubiquitous distribution, many pathological processes are associated with altered DPP-4 expression and activity. Besides the regulation of glucose metabolism, DPP-4 also exhibits many other systemic effects, and the inhibition of its activity might lead to cardiovascular and renal protection. Mechanisms underlying these protective effects of DPP-4 inhibition are ascribed to elevated bioavailability of its substrates, to impacts on mediators and signaling pathways that ameliorate cardiovascular and renal function through the suppression of oxidative stress, inflammation, fibrosis and apoptosis, improved endothelial function and tissue reparation...
May 28, 2018: Medicinal Research Reviews
Yang Liu, Xueting Yao, Ling Song, Hongzhong Liu, Qian Zhao, Ji Jiang, Gang Ni, Chongtie Shi, Xifeng Ma, Huimin Zhou, Dongyang Liu, Pei Hu
Imigliptin has been reported as a novel dipeptidyl-peptidase-IV (DPP-4) inhibitor to treat type 2 Diabetes Mellitus (T2DM), and is currently being tested in clinical trials. In the first human clinical study, imigliptin was well tolerated and proved to be a potent DPP-4 inhibitor. Considering its potential therapeutic benefits and promising future, it is of great importance to study the metabolite profiles in the early stage of drug development. In the present study, a robust and reliable analytical method based on the ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method combined with MassLynx software was established to investigate the characterization of metabolites of imigliptin in human and rat plasma, urine and feces after oral administration...
May 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
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