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Alexandre Baptista, Inês Teixeira, Sónia Romano, António Vaz Carneiro, Julian Perelman
OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list...
October 17, 2016: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
Hao Liu, Yun Hu, Feng-Fei Li, Bing-Li Liu, Xiao-Fei Su, Jian-Hua Ma
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails. Variance of the glycated hemoglobin (HbA1c) response to DPP-4 inhibitions in patients with type 2 diabetes mellitus (T2DM) has been observed, but the characteristics which predict the response to DPP-4 inhibitor therapy are unclear. The aim of this study was to investigate the characteristics of α- and β-cell functions which might predict the efficacy of saxagliptin and facilitate personalization of treatment...
October 12, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Benjamin M Scirica, Deepak L Bhatt, Eugene Braunwald, Itamar Raz, Matthew A Cavender, KyungAh Im, Ofri Mosenzon, Jacob A Udell, Boaz Hirshberg, Pia S Pollack, Ph Gabriel Steg, Petr Jarolim, David A Morrow
Importance: Cardiac biomarkers provide insights into pathophysiologic processes and offer an attractive strategy for the assessment of cardiovascular risk. Objective: To assess the incremental prognostic value of biomarkers that reflect different pathophysiologic processes in patients with type 2 diabetes. Design, Setting, and Participants: The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 is a randomized, double-blind, placebo-controlled clinical trial that evaluated the safety of saxagliptin vs placebo in 16 492 outpatients with type 2 diabetes with overt cardiovascular disease (CVD) or multiple risk factors...
September 28, 2016: JAMA Cardiology
Junichi Ikeda, Naoya Kimoto, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17...
September 2016: Journal of Pharmacological Sciences
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
Rimke C Vos, Mariëlle Jp van Avendonk, Hanneke Jansen, Alexander N Goudswaard, Maureen van den Donk, Kees Gorter, Anneloes Kerssen, Guy Ehm Rutten
BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control...
September 18, 2016: Cochrane Database of Systematic Reviews
Lin Wang, Peicheng Li, Zhaosheng Tang, Xinfeng Yan, Bo Feng
The mechanisms underlying the weight-loss effect of GLP-1 receptor agonists need further elucidation. The present study was performed to explore the effects of liraglutide and saxagliptin on the composition of the gut microbiota. Mice were randomly treated with saxagliptin or liraglutide for eight weeks. Their metabolic profiles were assessed, and 454 pyrosequencing of 16s rRNA of faeces was performed. Liraglutide induced a smaller body weight gain in mice. The pyrosequencing showed that liraglutide, but not saxagliptin, substantially changed the overall structure of the gut microbiota as well as the relative abundance of weight-relevant phylotypes...
2016: Scientific Reports
Daisuke Yabe, Yutaka Seino
Incretin-based dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are newer choices of antidiabetic medications that are now most widely used worldwide. Preclinical study results suggest that the two drugs potentially exert benefits to prevent onsets and/or progressions of diabetes-related complications, such as myocardial infarctions and strokes. Outcomes of five clinical trials to evaluate the cardiovascular (CV) safety of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonist have been recently reported...
September 9, 2016: Journal of Diabetes Investigation
Yochai Birnbaum, Mandeep Bajaj, Jinqiao Qian, Yumei Ye
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor activation delays the progression of diabetic nephropathy (DN) in rodents. The NOD-like receptor 3 (Nlrp3) inflammasome plays an important role in DN. Dipeptidyl peptidase-4 inhibitors (DPP4I) inhibit the degradation of endogenous GLP-1 and various other active substances. We assessed whether DPP4I attenuates diabetes-induced activation of the inflammasome and progression of DN in mice with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM)...
2016: BMJ Open Diabetes Research & Care
Amanda M Farr, John J Sheehan, Brian M Davis, David M Smith
BACKGROUND: Adherence and persistence to antidiabetes medications are important to control blood glucose levels among individuals with type 2 diabetes mellitus (T2D). OBJECTIVES: The objective of this study was to compare adherence and persistence over a 12-month period between patients initiating saxagliptin and patients initiating linagliptin, two dipeptidyl peptidase-4 inhibitors. METHODS: This retrospective cohort study was conducted in MarketScan(®) Commercial and Medicare Supplemental claims databases...
2016: Patient Preference and Adherence
(no author information available yet)
No abstract text is available yet for this article.
August 16, 2016: Annals of Internal Medicine
Priyanka A Shah, Jaivik V Shah, Mallika Sanyal, Pranav S Shrivastav
A specific and rapid liquid chromatography-tandem mass spectrometry method is proposed for the simultaneous determination of metformin (MET), saxagliptin (SAXA) and its active metabolite, 5-hydroxy saxagliptin (5-OH SAXA) in human plasma. Sample preparation was accomplished from 50 μL plasma sample by solid-phase extraction using sodium dodecyl sulfate as an ion-pair reagent. Reversed-phase chromatographic resolution of analytes was possible within 3.5 min on ACE 5CN (150 × 4.6 mm, 5 μm) column using acetonitrile and10...
August 10, 2016: Biomedical Chromatography: BMC
Merlin C Thomas, Päivi M Paldánius, Rajeev Ayyagari, Siew Hwa Ong, Per-Henrik Groop
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Blisse Vakkalagadda, Susan Lubin, Laurie Reynolds, Dan Liang, Alan S Marion, Frank LaCreta, David W Boulton
PURPOSE: This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered. METHODS: Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments...
August 2016: Clinical Therapeutics
Abigail Tebboth, Sally Lee, Anna Scowcroft, Paula Bingham-Gardiner, Will Spencer, John Bolodeoku, Syed Wasi Hassan
PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)-4 inhibitors require dose adjustment in patients with T2DM and renal impairment, we aimed to understand how these treatments are prescribed in UK clinical practice, and to determine whether recommended dose adjustments are being made at initial prescription. METHODS: This retrospective, descriptive cohort study analyzed data from the Clinical Practice Research Datalink (CPRD)...
August 2016: Clinical Therapeutics
Zachary A Marcum, Johanna E Bellon, Jie Li, Walid F Gellad, Julie M Donohue
BACKGROUND: Medications to treat and prevent chronic disease have substantially reduced morbidity and mortality; however, their diffusion has been uneven. Little is known about prescribing of chronic disease medications by nurse practitioners (NPs) and physician assistants (PAs), despite their increasingly important role as primary care providers. Thus, we sought to conduct an exploratory analysis to examine prescribing of new chronic disease medications by NPs and PAs compared to primary care physicians (PCPs)...
2016: BMC Health Services Research
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
Stephan Matthaei, Naresh Aggarwal, Pedro Garcia-Hernandez, Nayyar Iqbal, Hungta Chen, Eva Johnsson, Alex Chin, Lars Hansen
AIMS: We previously reported greater reductions in glycated hemoglobin (A1C) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes and inadequate glycemic control with dapagliflozin 10 mg/d plus metformin after 24 weeks of treatment. Here we report results over 52 weeks of treatment. MATERIALS AND METHODS: Patients (mean baseline A1C 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on...
July 12, 2016: Diabetes, Obesity & Metabolism
Shira Perl, William Cook, Cheryl Wei, Nayyar Iqbal, Boaz Hirshberg
INTRODUCTION: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). The recommended dose of the dipeptidyl peptidase-4 inhibitor saxagliptin is 2.5 mg in patients with moderate or severe renal impairment (creatinine clearance ≤50 mL/min). In this post hoc analysis, we assessed the effect of saxagliptin 2.5 and 5 mg/day versus placebo on glycemic measures in patients with T2D and estimated glomerular filtration rate 45-60 mL/min/1.73 m(2). METHODS: Efficacy and safety data were pooled from nine 24-week, randomized, placebo-controlled clinical trials...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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