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P Sneha, C George Priya Doss
The pace of anti-diabetic drug discovery is very slow in spite of increasing rate of prevalence of Type 2 Diabetes which remains a major public health concern. Though extensive research steps are taken in the past decade, yet craves for better of new treatment strategies to overcome the current scenario. One such general finding is the evolution of gliptins which discriminately inhibits DPP4 (Dipeptidyl peptidase-4) enzyme. Although the mechanism of action of gliptin is highly target oriented and accurate, still its long-term use stands unknown...
October 12, 2016: Life Sciences
Shilpa, Mishra Arvind, Mittal M
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
Ivan Tkáč, Itamar Raz
OBJECTIVE: Data on the possible relationship of gliptin treatment to the incidence of acute pancreatitis have been controversial. The aim of the current study was to combine data on the incidence of acute pancreatitis from three large randomized controlled trials. RESEARCH DESIGN AND METHODS: Three trials designed to test cardiovascular safety and efficacy of add-on treatment with a gliptin were included in the analysis, as follows: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin)...
September 22, 2016: Diabetes Care
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Eun Ju Bae
Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are an emerging class of antidiabetic drugs that constitutes approximately fifty percent of the market share of the oral hypoglycemic drugs. Its mechanism of action for lowering blood glucose is essentially via inhibition of the rapid degradation of incretin hormones, such as glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide (GIP), thus the plasma concentration of GLP-1 increases, which promotes insulin secretion from the pancreatic β cells and suppresses glucagon secretion from the α cells...
August 2016: Archives of Pharmacal Research
Havva Ozge Keseroglu, Gamze Taş-Aygar, Müzeyyen Gönül, Ozay Gököz, Sibel Ersoy-Evans
Bullous pemfigoid (BP), an autoimmune disorder, can also be induced by some medications. Vildagliptin is a new drug used to treat diabetes mellitus (DM). Recently, a few cases of vildagliptin-induced BP have been described in the literature. We report a patient with BP in which vildagliptin was thought to be as a possible causative agent. The awareness of BP development risk during gliptin therapy can prevent unnecessary usage of systemic drugs with serious side effects.
August 11, 2016: Cutaneous and Ocular Toxicology
Gisela Schnapp, Thomas Klein, Yvette Hoevels, Remko A Bakker, Herbert Nar
The binding kinetics and thermodynamics of dipeptidyl peptidase (DPP)-4 inhibitors (gliptins) were investigated using surface plasmon resonance and isothermal titration calorimetry. Binding of gliptins to DPP-4 is a rapid electrostatically driven process. Off-rates were generally slow partly because of reversible covalent bond formation by some gliptins, and partly because of strong and extensive interactions. Binding of all gliptins is enthalpy-dominated due to strong ionic interactions and strong solvent-shielded hydrogen bonds...
August 25, 2016: Journal of Medicinal Chemistry
André J Scheen
INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. AREA COVERED: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations...
July 29, 2016: Expert Opinion on Drug Metabolism & Toxicology
Julia Hippisley-Cox, Carol Coupland
OBJECTIVE:  To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones). DESIGN:  Open cohort study. SETTING:  1243 general practices contributing data to the QResearch database in England. PARTICIPANTS:  469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015...
2016: BMJ: British Medical Journal
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
André J Scheen
Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach...
July 2016: Diabetes Research and Clinical Practice
(no author information available yet)
No abstract text is available yet for this article.
April 2016: Prescrire International
M García, M A Aranburu, I Palacios-Zabalza, U Lertxundi, C Aguirre
WHAT IS KNOWN AND OBJECTIVE: Bullous pemphigoid has been reported in association with gliptins. We describe a case, review the literature and analyse all cases of bullous pemphigoid recorded in the European pharmacovigilance database, EudraVigilance. CASE SUMMARY: A 74-year-old woman, treated with vildagliptin/metformin for 12 months, developed bullous pemphigoid, confirmed by skin biopsy. The symptoms resolved within 7 months after vildagliptin/metformin withdrawal...
June 2016: Journal of Clinical Pharmacy and Therapeutics
Jiří Hradec, Eva Račická
Type 2 diabetes mellitus represents a serious medical, social and economic problem, since it has become a pandemic in recent years, affecting up to 1/3 of the Czech population in old age. It is the clinically most significant metabolic disease in older age. A pharmacotherapeutic approach needs to be adjusted to the presence of multiple comorbidities in the elderly and to the patients ability to cooperate with treatment, and owing to the feared hypoglycemia which may contribute to increased morbidity, it detracts from the quality of life and limits the possibilities of treatment in many cases...
March 2016: Vnitr̆ní Lékar̆ství
Ivan Tkáč
Pharmacogenetics is the study of how genes (individual genotypes) affect a persons response to drugs. At present, recommendations made about the treatment of some monogenic forms of diabetes are based on genetic diagnostics. The first studies in the field of pharmacogenetics of oral antidiabetics have now been published which have identified associations of individual genetic variants with response to treatment. The response to sulfonylurea derivatives was significantly associated with the variants KCNJ11/ABCC8, TCF7L2 and CYP2C9...
March 2016: Vnitr̆ní Lékar̆ství
Ivan Tkáč, Ivana Gotthardová
Incretin effect enhancers are drugs used in the treatment of Type 2 diabetes and include GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (gliptins). Variants in several genes were shown to be involved in the physiology of incretin secretion. Only two gene variants have evidence also from pharmacogenetic studies. TCF7L2 rs7903146 C>T and CTRB1/2 rs7202877 T>G minor allele carriers were both associated with a smaller reduction in HbA1c after gliptin treatment when compared with major allele carriers...
May 2016: Pharmacogenomics
M Javorský, I Gotthardová, L Klimčáková, M Kvapil, J Židzik, Z Schroner, P Doubravová, I Gala, I Dravecká, I Tkáč
Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment...
September 2016: Diabetes, Obesity & Metabolism
Harald Staiger, Elke Schaeffeler, Matthias Schwab, Hans-Ulrich Häring
Many clinical treatment studies have reported remarkable interindividual variability in the response to pharmaceutical drugs, and uncovered the existence of inadequate treatment response, non-response, and even adverse drug reactions. Pharmacogenetics addresses the impact of genetic variants on treatment outcome including side-effects. In recent years, it has also entered the field of clinical diabetes research. In modern type 2 diabetes therapy, metformin is established as first-line drug. The latest pharmaceutical developments, including incretin mimetics, dipeptidyl peptidase 4 inhibitors (gliptins), and sodium/glucose cotransporter 2 inhibitors (gliflozins), are currently experiencing a marked increase in clinical use, while the prescriptions of α-glucosidase inhibitors, sulfonylureas, meglitinides (glinides), and thiazolidinediones (glitazones) are declining, predominantly because of reported side-effects...
October 2015: Review of Diabetic Studies: RDS
A Zeyfang
BACKGROUND: A majority of older people with type 2 diabetes are multimorbid, frail or have limitations in functions. Polypharmacotherapy is unfortunately a frequent occurrence and dangerous. In particular the administration of antihyperglycemic therapy must be carefully weighed up against the risks associated with hypoglycemia. AIM: The conditions and characteristics of older persons with diabetes are highlighted with respect to the use of individualized therapy of diabetes...
May 2016: Der Internist
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