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Dipeptidyl peptidase-4 inhibitor Drug class

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https://www.readbyqxmd.com/read/28726152/cardiovascular-outcome-trial-update-in-diabetes-new-evidence-remaining-questions
#1
REVIEW
Rebecca Herbst, Wilburn Bolton, Afreen Shariff, Jennifer B Green
PURPOSE OF REVIEW: Seven trials of new agents to treat type 2 diabetes (T2DM) have been performed to assess cardiovascular (CV) safety. A significant amount of information regarding the effects of drugs in three classes is available, with new data from multiple other trials expected shortly. This article provides a summary of recently completed trials. RECENT FINDINGS: The dipeptidyl peptidase-4 inhibitors studied thus far do not alter the risk of major adverse CV events (MACE)...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#2
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
https://www.readbyqxmd.com/read/28661561/comparative-safety-of-pioglitazone-versus-clinically-meaningful-treatment-alternatives-on-the-risk-of-bladder-cancer-in-older-us-adults-with-type-2-diabetes
#3
Elizabeth M Garry, John B Buse, Jennifer L Lund, Virginia Pate, Til Stürmer
AIMS: Compare bladder cancer incidence between patients initiating pioglitazone and patients initiating dipeptidyl-peptidase-4 inhibitors [DPP-4 s] or sulfonylureas. METHODS: We identified Medicare beneficiaries aged >65 initiating pioglitazone (N = 38,700), DPP-4 s (N = 82,552), or sulfonylureas (N = 126,104) 2007-2014 after at least 6 months without prescriptions for these drug classes. Patients were followed from second prescription until bladder cancer outcome (2 claims within 60 days) using a 6-month induction/latency period, censoring for treatment change, death, or end of 2014...
June 29, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#4
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28631762/-safety-and-tolerability-of-oral-hypoglycemic-therapies-in-type-2-diabetes-mellitus-patients-at-high-cardiovascular-risk
#5
Giuseppe Ambrosio, Gaetano M De Ferrari, Massimo Federici, Pasquale Perrone Filardi
Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia...
June 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28589493/a-randomized-placebo-controlled-trial-evaluating-the-safety-and-efficacy-of-adding-omarigliptin-to-antihyperglycemic-therapies-in-japanese-patients-with-type-2-diabetes-and-inadequate-glycemic-control
#6
Ira Gantz, Taro Okamoto, Yuka Ito, Asako Sato, Kotoba Okuyama, Edward A O'Neill, Samuel S Engel, Eseng Lai
INTRODUCTION: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients. METHODS: A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q...
June 6, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28459036/consensus-statement-on-dose-modifications-of-antidiabetic-agents-in-patients-with-hepatic-impairment
#7
REVIEW
Kalyan Kumar Gangopadhyay, Parminder Singh
Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia...
March 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28435305/glucagon-like-peptide-1-receptor-agonists-a-systematic-review-of-comparative-effectiveness-research
#8
REVIEW
Philip A Levin, Hiep Nguyen, Eric T Wittbrodt, Seoyoung C Kim
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. OBJECTIVE: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. METHODS: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-of-acute-pancreatitis-and-or-pancreatic-cancer-reassuring-data-from-cardio-vascular-outcome-trials
#9
LETTER
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
No abstract text is available yet for this article.
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28420715/role-of-soluble-and-membrane-bound-dipeptidylpeptidase-4-in-diabetic-nephropathy
#10
Ahmed A Hasan, Berthold Hocher
Diabetic nephropathy is one of the most frequent, devastating, and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might have in addition reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians...
April 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28397367/continuous-glucose-monitoring-reveals-hypoglycemia-risk-in-elderly-patients-with-type-2-diabetes-mellitus
#11
Takahiro Ishikawa, Masaya Koshizaka, Yoshiro Maezawa, Minoru Takemoto, Yoshiharu Tokuyama, Toshihiro Saito, Koutaro Yokote
AIMS/INTRODUCTION: The incidence of type 2 diabetes is higher in elderly patients, in whom this disease is associated with dementia, falling, stroke and death. We utilized a continuous glucose monitoring device to analyze the relationship between hypoglycemia and diabetes treatments to identify risk factors for hypoglycemia (defined as a blood glucose level <70 mg/dL). MATERIALS AND METHODS: We classified 170 patients aged ≥65 years with type 2 diabetes who were receiving steady-state medication (29 of whom were inpatients) into hypoglycemic and non-hypoglycemic groups, and compared their glycosylated hemoglobin levels, treatment types, continuous glucose monitoring data and other parameters...
April 11, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28393419/synthesis-and-evaluation-of-novel-1-2-4-triazolo-5-1-c-1-2-4-triazines-and-pyrazolo-5-1-c-1-2-4-triazines-as-potential-antidiabetic-agents
#12
Vladimir L Rusinov, Irina M Sapozhnikova, Anastasiya M Bliznik, Oleg N Chupakhin, Valery N Charushin, Alexander A Spasov, Pavel M Vassiliev, Valentina A Kuznetsova, Andrey I Rashchenko, Denis A Babkov
Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers...
April 10, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28369870/antihyperglycemic-drugs-use-and-new-onset-atrial-fibrillation-in-elderly-patients
#13
Hung-Yi Chen, Fu-Yu Yang, Gwo-Ping Jong, Yi-Sheng Liou
BACKGROUND: Antihyperglycemic drugs have been linked to new-onset atrial fibrillation (NAF). However, the effect of the different classes of antihyperglycemic drugs on the development of NAF in elderly patients has not been well studied. In this study, we investigated the association between different classes of antihyperglycemic drugs and NAF in elderly patients. MATERIALS AND METHODS: This was a nested case-control study performed using the database of National Health Insurance programme in Taiwan...
March 30, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28356718/sodium-glucose-cotransporter-2-inhibitors-combined-with-dipeptidyl-peptidase-4-inhibitors-in-the-management-of-type-2-diabetes-a-review-of-current-clinical-evidence-and-rationale
#14
REVIEW
Sayf A Yassin, Vanita R Aroda
Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial cardiometabolic disorder. Almost half of adults with diabetes fail to achieve their recommended glucose control target. This has prompted some clinicians to advocate the use of more intensive initial therapy, including the use of combination therapy to target multiple physiologic defects in diabetes with the goal of achieving and sustaining glucose control. Numerous options exist for combining the various classes of glucose-lowering agents in the treatment of T2DM...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28342563/type-2-diabetes-mellitus-treatment-patterns-across-europe-a-population-based-multi-database-study
#15
Jetty A Overbeek, Edith M Heintjes, Daniel Prieto-Alhambra, Patrick Blin, Régis Lassalle, Gillian C Hall, Francesco Lapi, Elisa Bianchini, Niklas Hammar, Irene D Bezemer, Ron M C Herings
PURPOSE: The aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. METHODS: Prescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns...
March 22, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28326532/common-drug-side-effects-and-drug-drug-interactions-in-elderly-adults-in-primary-care
#16
Susan E Merel, Douglas S Paauw
Prescribing medications, recognizing and managing medication side effects and drug interactions, and avoiding polypharmacy are all essential skills in the care of older adults in primary care. Important side effects of medications commonly prescribed in older adults (statins, proton pump inhibitors, trimethoprim-sulfamethoxazole and fluoroquinolone antibiotics, zolpidem, nonsteroidal antiinflammatory drugs, selective serotonin reuptake inhibitors, dipeptidyl peptidase 4 inhibitors) were reviewed. Important drug interactions with four agents or classes (statins, warfarin, factor Xa inhibitors, and calcium channel blockers) are discussed...
July 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28230454/adherence-persistence-and-health-care-costs-for-patients-receiving-dipeptidyl-peptidase-4-inhibitors
#17
Karen L Rascati, Karen Worley, Yunus Meah, Damian Everhart
BACKGROUND: The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications. OBJECTIVE: To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors. METHODS: Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28201967/dipeptidyl-peptidase-4-inhibitor-induced-angioedema-an-overlooked-and-potentially-lethal-adverse-drug-reaction
#18
Susanne Irene Scott, Michelle Fog Andersen, Lise Aagaard, Christian Von Buchwald, Eva Rye Rasmussen
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are anti-diabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28178698/dipeptidyl-peptidase-4-inhibitors-in-chronic-kidney-disease-a-systematic-review-of-randomized-clinical-trials
#19
Simon R Walker, Paul Komenda, Suhail Khojah, Wafa Al-Tuwaijri, Kerry MacDonald, Brett Hiebert, Neil Tangri, Stewart W D Nadurak, Thomas W Ferguson, Claudio Rigatto, Navdeep Tangri
BACKGROUND: Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population. METHODS: We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1...
2017: Nephron
https://www.readbyqxmd.com/read/28128944/design-and-elaboration-of-a-tractable-tricyclic-scaffold-to-synthesize-druglike-inhibitors-of-dipeptidyl-peptidase-4-dpp-4-antagonists-of-the-c-c-chemokine-receptor-type-5-ccr5-and-highly-potent-and-selective-phosphoinositol-3-kinase-%C3%AE-pi3k%C3%AE-inhibitors
#20
Carolin Schwehm, Barrie Kellam, Aimie E Garces, Stephen J Hill, Nicholas D Kindon, Tracey D Bradshaw, Jin Li, Simon J F Macdonald, James E Rowedder, Leigh A Stoddart, Michael J Stocks
A novel molecular scaffold has been synthesized, and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies, we have shown use of the tricyclic scaffold to synthesize potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs...
February 23, 2017: Journal of Medicinal Chemistry
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