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Roberto Negro, Eupremio Luigi Greco, Giacomo Greco
AIM: We investigated the effect of alogliptin and gliclazide on endothelial progenitor cells (EPCs) in type 2 diabetes. METHODS: Eighty patients with type 2 diabetes and HbA1c between 7.5% and 8.5% were randomized to receive either alogliptin (25 mg/daily) or gliclazide extended-release (30 mg/daily for HbA1c 7.5-8.0% and 60 mg/daily for HbA1c 8.0-8.5%) in combination with metformin for 4 months. At baseline and 4 months, clinical and laboratory parameters of EPCs were determined...
March 20, 2018: Experimental and Clinical Endocrinology & Diabetes
Shota Hodono, Akihiro Shimokawa, Neil J Stewart, Yukiko Yamauchi, Renya Nishimori, Mami Yamane, Hirohiko Imai, Hideaki Fujiwara, Atsuomi Kimura
PURPOSE: High Mobility Group Box1 (HMGB1), which is one of the damage-associated molecular pattern molecules relating to various inflammatory diseases, has gained interest as a therapeutic target because of its involvement in wound healing processes. In the present study, we investigated HMGB1 as a potential therapeutic target in a model of lung fibrosis using a preclinical hyperpolarized129 Xe (HPXe) MRI system. METHODS: Lung injury was induced by intra-peritoneal injection of bleomycin (BLM) in 19 mice...
March 9, 2018: Magnetic Resonance in Medical Sciences: MRMS
Hiroshi Tobita, Shuichi Sato, Tomotaka Yazaki, Tsuyoshi Mishiro, Norihisa Ishimura, Shunnji Ishihara, Yoshikazu Kinoshita
Pioglitazone (PIO) has been reported to be effective for nonalcoholic fatty liver disease (NAFLD) and alogliptin (ALO) may have efficacy against NAFLD progression in patients with type 2 diabetes mellitus (T2DM). The present study examined the effectiveness of ALO in a rodent model of NAFLD and diabetes mellitus. KK‑Ay mice were used to produce an NAFLD model via administration of a choline‑deficient (CD) diet. To examine the effects of alogliptin, KK‑Ay mice were provided with a CD diet with 0.03% ALO and/or 0...
March 1, 2018: Molecular Medicine Reports
André Jacques Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) are generally considered as glucose-lowering agents with a safe profile in type 2 diabetes. Areas covered: An updated review of recent safety data from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance reports regarding alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin, with a special focus on risks of hypoglycemia, pancreatitis and pancreatic cancer, major cardiovascular events, hospitalisation for heart failure and other new safety issues, such as bone fractures and arthralgia...
April 2018: Expert Opinion on Drug Safety
Michael Fralick, Jerry Avorn, Jessica M Franklin, Abdurrahman Abdurrob, Aaron S Kesselheim
BACKGROUND: A run-in phase is often employed prior to randomization in a clinical trial to exclude non-adherent patients, placebo responders, active drug non-responders, or patients who do not tolerate the active drug. This may impact the generalizability of trial results. OBJECTIVE: To determine if clinical outcomes differed between randomized controlled trials with run-in phases compared with randomized controlled trials of the same medication without run-in phases...
February 15, 2018: Journal of General Internal Medicine
Yuichiro Amano, Shuntarou Tsuchiya, Mayumi Imai, Kimio Tohyama, Jun Matsukawa, Osamu Isono, Hironobu Yasuno, Kazuaki Enya, Emiko Koumura, Hiroshi Nagabukuro
This study aimed to evaluate the effects of combination therapy with a dipeptidyl peptidase-4 inhibitor, alogliptin, and a peroxisome proliferator-activated receptor-γ agonist, pioglitazone, in a preclinical model of nonalcoholic steatohepatitis using low-density lipoprotein receptor-knockout mice fed a modified choline-deficient l-amino acid-defined diet. Monotherapy with either alogliptin (10-200 mg/kg) or pioglitazone (6-20 mg/kg) significantly decreased hepatic triglyceride content and fibrosis. The concomitant treatment of alogliptin (30 mg/kg), pioglitazone (20 mg/kg) also decreased hepatic triglyceride and hepatic collagen-I mRNA at greater extent compared to monotherapy...
February 8, 2018: Biochemical and Biophysical Research Communications
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, exenatide, lixisenatide) have recently been used as anti-diabetes drugs. We examined relationships of the binding occupancy of GLP-1 receptors (Φ) and their clinical efficacy after administration of GLP-1 receptor agonists. Next, by focusing on changes of GLP-1 concentration after administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, alogliptin, sitagliptin, linagliptin), we analyzed the relationship between Φ and clinical efficacy...
2018: Biological & Pharmaceutical Bulletin
Alberto Palazzuoli, Elena Ceccarelli, Gaetano Ruocco, Ranuccio Nuti
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate...
January 23, 2018: Heart Failure Reviews
Katherine G Garlo, William B White, George L Bakris, Faiez Zannad, Craig A Wilson, Stuart Kupfer, Muthiah Vaduganathan, David A Morrow, Christopher P Cannon, David M Charytan
BACKGROUND AND OBJECTIVES: Biomarkers may improve identification of individuals at risk of eGFR decline who may benefit from intervention or dialysis planning. However, available biomarkers remain incompletely validated for risk stratification and prediction modeling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1 (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367 individuals with type 2 diabetes mellitus and recent acute coronary syndromes enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial...
March 7, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Yoko Irie, Naoto Katakami, Tomoya Mita, Mitsuyoshi Takahara, Taka-Aki Matsuoka, Masahiko Gosho, Hirotaka Watada, Iichiro Shimomura
INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray-scale median (GSM) reflects its composition and low-GSM plaque is considered to be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue characteristics of the carotid wall, in patients with type 2 diabetes (T2DM). METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A trial, a randomized controlled trial that demonstrated the beneficial effect of alogliptin treatment on the progression of carotid intima-media thickness in patients with T2DM with no past history of apparent cardiovascular disease...
January 12, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Siva Sankar Murthy Bandaru, Shatrughn Bhilare, Nicolas Chrysochos, Vijay Gayakhe, Ivan Trentin, Carola Schulzke, Anant R Kapdi
A mild and highly efficient catalytic amination procedure for chloroheteroarenes at ambient temperature using the Pd/PTABS catalytic system is reported. The protocol is selective for the amination of chloroheteroarenes using secondary amines such as piperidine, pyrrolidine, and several others. The exceptional mildness of the developed protocol is beneficial for the synthesis of a crucial Buparlisib intermediate as well as the formal synthesis of Alogliptin in competitive yields.
January 5, 2018: Organic Letters
Koichi Kanozawa, Yuichi Noguchi, Souichi Sugahara, Satoko Nakamura, Hirohisa Yamamoto, Keiko Kaneko, Rika Kono, Saeko Sato, Tomonari Ogawa, Hajime Hasegawa, Shigehiro Katayama
BACKGROUND: We conducted the multicenter, prospective, open-label study in type 2 diabetic (T2DM) patients with renal dysfunction, to clarify the efficacy and the safety in relation to renal function and glycemic control, and the economic effect when other dipeptidyl peptidase-4 (DPP-4) inhibitors were switched to a small dose of sitagliptin depending on their renal function. METHODS: Vildagliptin, alogliptin, or linagliptin received for more than 2 months were changed to sitagliptin at 25 or 12...
December 23, 2017: Clinical and Experimental Nephrology
Wen-Qin Guo, Lang Li, Qiang Su, Wei-Ran Dai, Zi-Liang Ye
BACKGROUND: Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments. METHODS: A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Roberto Negro, Eupremio Luigi Greco, Giacomo Greco
Background: It is postulated that the ability of dipeptidyl peptidase-4 inhibitors (DPP-4-i) to increase circulating endothelial progenitor cells (EPCs) may be at least partly mediated by active stromal cell-derived factor 1α (SDF-1α) (a pivotal mediator of stem cell mobilization from the bone marrow). As other DPP-4-i were demonstrated to increase EPC concentrations, in this study, we sought to investigate the ability of the DPP-4-i alogliptin in modifying EPCs and SDF-1α, in patients with good and poor diabetes control...
2017: Clinical Medicine Insights. Endocrinology and Diabetes
Wafaa A Zaghary, Shereen Mowaka, Mostafa A Hassan, Bassam M Ayoub
Multifaceted comparative analytical methods for trelagliptin (TRL) were investigated, applied to ZAFATEK tablets and HPLC-UV was selected for a degradation kinetic study. UPLC-MS/MS (Method I), UPLC-UV (Method II), HPLC-UV (Method III), UHPLC-UV (Method IV) and direct UV (Method V) methods were developed. Methods (I-V) showed satisfactory results using TRL concentration ranges of 50-800 ng/mL, 2.5-80 μg/mL, 5-100 μg/mL, 5-100 μg/mL and 5-50 μg/mL, respectively. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 358...
December 8, 2017: Scientific Reports
Jun Yang, Chao Huang, Shanshan Wu, Yang Xu, Ting Cai, Sanbao Chai, Zhirong Yang, Feng Sun, Siyan Zhan
AIM: The association between dipeptidyl peptidase-4 inhibitors (DPP-4is), a class of anti-diabetes, and bone fracture in patients with type 2 diabetes mellitus (T2DM) is unknown. This meta-analysis aimed to systematically evaluate the effects of DPP-4is on bone fracture in T2DM patients. METHODS: We searched the Cochrane Library, Embase, Medline and from inception through April 28th, 2016 to identify randomized controlled trials (RCTs) that compared DPP-4is with placebo or other anti-diabetes in T2DM patients...
2017: PloS One
Danyan Chen, Xiaolong Huang, Hua Gan, Xiaogang Du, Song Lu, Rongxi Huang, Ke Liu, Binghan Zhang
In the present study, we evaluated the curative effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor alogliptin combined with motor imagery under hyperbaric oxygen in diabetic nephropathy (DN) with silent cerebral infarction (SCI). Two-hundred newly diagnosed DN patients with and without SCI were included. The SCI patients were divided into two treatment groups: Alogliptin (A group, n=50) and alogliptin combined with motor imagery under hyperbaric oxygen (B group, n=50). The degrees of neurocognitive dysfunction were evaluated at baseline and after 6 months of treatment...
November 2017: Biomedical Reports
David Paul, Lingesh Allakonda, Amit Sahu, Shruti Surendran, Nanjappan Satheeshkumar
Perampanel (PER) is a novel AMPA receptor antagonist for antiepileptic therapy and is prospective for the treatment of other neurological disorders. A highly sensitive and rapid UHPLC-QTOF-MS method was developed for the quantification of PER in plasma/brain homogenate of SD rat with alogliptin as an internal standard (IS). Chromatographic separation was carried out on an Acquity UPLC HSS Cyano column (100mm×2.1mm, 1.8μm) using gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0...
November 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
Ahmed M Kabel
The aim of this study was to assess the effect of alogliptin and/or zinc on doxorubicin (DOX)-induced testicular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; DOX; DOX+Zinc; DOX+Alogliptin; DOX+Carboxymethyl cellulose and DOX+Zinc+Alogliptin. Testis weight, testicular functions, serum testosterone, luteinizing hormone, follicle stimulating hormone and zinc were measured. Also, testicular tissue zinc, 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, antioxidant enzymes, pro-inflammatory cytokines, transforming growth factor beta 1 (TGF-β1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and sperm characteristics were assessed...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
You-Cheol Hwang, David A Morrow, Christopher P Cannon, Yuyin Liu, Richard Bergenstal, Simon Heller, Cyrus Mehta, William Cushman, George L Bakris, Faiez Zannad, William B White
OBJECTIVE: We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high-sensitivity C-reactive protein (hsCRP) level and low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and recent acute coronary syndrome. RESEARCH DESIGN AND METHODS: Study participants enrolled in the EXAMINE trial, were stratified by baseline hsCRP levels (<1, 1-3, and >3 mg/l) and were also sub-divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/l) and achieved LDL-C (<70 or ≥70 mg/dl) levels...
October 24, 2017: Diabetes, Obesity & Metabolism
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