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https://www.readbyqxmd.com/read/29769203/early-and-chronic-dipeptidyl-peptidase-iv-inhibition-and-cardiovascular-events-in-patients-with-type-2-diabetes-mellitus-after-an-acute-coronary-syndrome-a-landmark-analysis-of-the-examine-trial
#1
Abhinav Sharma, Christopher P Cannon, William B White, Yuyin Liu, George L Bakris, William C Cushman, Faiez Zannad
BACKGROUND: Antihyperglycemic therapies may increase the risk of cardiovascular events including hospitalization for heart failure. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high-risk period following an acute coronary syndrome (ACS). METHODS AND RESULTS: The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial randomized 5380 patients who were 15 to 90 days post ACS to the dipeptidyl dipeptidase-IV (DPP-IV) inhibitor alogliptin versus placebo; mean follow-up was 18 months...
May 16, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29762878/risk-of-hypoglycemia-after-concomitant-use-of-antidiabetic-antihypertensive-and-antihyperlipidemic-medications-a-database-study
#2
Masahiko Gosho
Hypoglycemia is the most important complication of antidiabetic medications. Most patients with diabetes mellitus take multiple medications. In this study, we explored clinical drug-drug interactions that result in hypoglycemia by analyzing the Japanese Adverse Drug Event Report (JADER) database. The primary outcome was the report of hypoglycemia. The Norén and Gosho methods, which quantitatively measure the discrepancy between the observed and expected number of adverse events under the combination of 2 drugs, were used as the criteria for detecting drug-drug interactions...
May 15, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#3
REVIEW
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29682682/molecular-and-clinical-roles-of-incretin-based-drugs-in-patients-with-heart-failure
#4
REVIEW
Bassant Orabi, Rasha Kaddoura, Amr S Omar, Cornelia Carr, Abdulaziz Alkhulaifi
Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors produce some beneficial and deleterious effects in diabetic patients not mediated by their glycemic lowering effects, and there is a need for better understanding of the molecular basis of these effects. They possess antioxidant and anti-inflammatory effects with some direct vasodilatory action (animal and human trial data) that may indirectly influence heart failure (HF). Unlike GLP-1R agonists, signaling for HF adverse effects was observed with two DPP-4 inhibitors, saxagliptin and alogliptin...
April 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29679391/cardiovascular-effects-of-sitagliptin-an-anti-diabetes-medicine
#5
REVIEW
Yi Zhou, Zhiying Guo, Wenjing Yan, Wen Wang
Dipeptidyl-peptidase-4 (DPP-4) inhibitors, as the most recent available anti-diabetic agents, were generally used in clinical treatment of type 2 diabetes (T2DM). In addition to anti-diabetic effects, the five most widely used DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) also exert cardiovascular protective effects. In recent years, increasing studies suggest that sitagliptin shows pleiotropic impacts towards the cardiovascular system either with or without diabetes...
April 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29652078/total-cardiovascular-events-analysis-of-the-examine-trial-in-patients-with-type-2-diabetes-and-recent-acute-coronary-syndrome
#6
Matthew A Cavender, William B White, Yuyin Liu, Joseph M Massaro, Richard M Bergenstal, Cyrus R Mehta, Faiez Zannad, Simon Heller, William C Cushman, Christopher P Cannon
BACKGROUND: Alogliptin, a dipeptidyl-peptidase 4 inhibitor, is approved for the treatment of patients with type 2 diabetes. EXAMINE was a randomized-controlled clinical trial designed to demonstrate the cardiovascular safety of alogliptin. In the trial, 5380 patients with established T2DM who had a recent ACS event (between 15-90 days) were randomized to treatment with either alogliptin or placebo. HYPOTHESIS: To better understand and describe the cardiovascular (CV) safety of alogliptin, we analyzed data from the EXAMINE randomized clinical trial to determine whether treatment with alogliptin affected recurrent and total CV events...
April 13, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29581078/alogliptin-in-patients-with-type-2-diabetes-on-metformin-and-sulfonylurea-therapies-in-the-examine-trial
#7
William B White, Simon R Heller, Christopher P Cannon, Heena Howitt, Kamlesh Khunti, Richard M Bergenstal
BACKGROUND: We evaluated the antihyperglycemic efficacy and safety of adding the dipeptidyl dipeptidase-4 inhibitor alogliptin to metformin and sulphonylurea in the treatment of type 2 diabetes in the EXAMINE Trial. METHODS: Patients with type 2 diabetes and recent acute coronary syndrome were randomized to alogliptin or placebo and standard of care. Participants were followed for up to 40 (median 18) months. In a subgroup taking metformin and sulphonylurea at baseline, we evaluated change from baseline in HbA1c, adverse events, cardiovascular outcomes, laboratory data, and other safety parameters...
March 23, 2018: American Journal of Medicine
https://www.readbyqxmd.com/read/29558784/alogliptin-and-gliclazide-similarly-increase-circulating-endothelial-progenitor-cells-in-type-2-diabetes-patients
#8
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
https://www.readbyqxmd.com/read/29526883/ethyl-pyruvate-improves-pulmonary-function-in-mice-with-bleomycin-induced-lung-injury-as-monitored-with-hyperpolarized-129-xe-mr-imaging
#9
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 hyperpolarized 129 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
https://www.readbyqxmd.com/read/29512720/alogliptin-alleviates-hepatic-steatosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease-by-promoting-cpt1a-expression-via-thr172-phosphorylation-of-ampk%C3%AE-in-the-liver
#10
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...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29468916/the-safety-of-gliptins-updated-data-in-2018
#11
REVIEW
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
https://www.readbyqxmd.com/read/29450684/application-and-impact-of-run-in-studies
#12
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...
May 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29428719/combination-effects-of-alogliptin-and-pioglitazone-on-steatosis-and-hepatic-fibrosis-formation-in-a-mouse-model-of-non-alcoholic-steatohepatitis
#13
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 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29386477/evaluation-of-drug-efficacy-of-glp-1-receptor-agonists-and-dpp-4-inhibitors-based-on-target-molecular-binding-occupancy
#14
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
https://www.readbyqxmd.com/read/29359260/clinical-impact-of-oral-antidiabetic-medications-in-heart-failure-patients
#15
REVIEW
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
https://www.readbyqxmd.com/read/29339356/kidney-biomarkers-and-decline-in-egfr-in-patients-with-type-2-diabetes
#16
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
https://www.readbyqxmd.com/read/29330812/evaluation-of-the-effect-of-alogliptin-on-tissue-characteristics-of-the-carotid-wall-subanalysis-of-the-spead-a-trial
#17
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...
February 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29303597/pd-ptabs-catalyst-for-room-temperature-amination-of-heteroarenes
#18
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 19, 2018: Organic Letters
https://www.readbyqxmd.com/read/29275488/the-renoprotective-effect-and-safety-of-a-dpp-4-inhibitor-sitagliptin-at-a-small-dose-in-type-2-diabetic-patients-with-a-renal-dysfunction-when-changed-from-other-dpp-4-inhibitors-real-trial
#19
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
https://www.readbyqxmd.com/read/29241903/effect-of-dipeptidyl-peptidase-4-inhibitors-on-heart-failure-a-network-meta-analysis
#20
COMPARATIVE STUDY
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
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