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Dipeptidyl peptidase-4 inhibitor Drug class

Milton Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
March 12, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
Keizo Kanasaki
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine...
February 28, 2018: Clinical Science (1979-)
Soo Lim, Kyoung Min Kim, Michael A Nauck
Several new glucose-lowering medications have been approved, such as dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors. Among GLP-1RAs, lixisenatide, a short-acting drug, did not show cardiovascular (CV) benefits in patients with Type 2 diabetes mellitus (T2D) and acute coronary syndrome. Extended-release exenatide was also not significantly better for CV outcomes. By contrast, once daily liraglutide and once weekly semaglutide, both long-acting GLP-1RAs, decreased the incidence of major adverse CV events and mortality...
February 17, 2018: Trends in Endocrinology and Metabolism: TEM
Aine M McKillop, Claire L Stevenson, Brian M Moran, Yasser H A Abdel-Wahab, Peter R Flatt
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < ...
February 2018: Peptides
Carolyn F Deacon
Dipeptidyl peptidase-4 (DPP-4) inhibitors are now a widely used, safe and efficacious class of antidiabetic drugs, which were developed prospectively using a rational drug design approach based on a thorough understanding of the endocrinology and degradation of glucagon-like peptide-1 (GLP-1). GLP-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability...
February 2018: Peptides
Vasiliki Bistola, Vaia Lambadiari, George Dimitriadis, Ioannis Ioannidis, Konstantinos Makrilakis, Nikolaos Tentolouris, Apostolos Tsapas, John Parissis
Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease...
January 31, 2018: Heart Failure Reviews
Abhiroop Chakravarty, Mohini Rastogi, Praveen Dhankhar, Kelly Bell
OBJECTIVE: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin. METHODS: A short-term decision-analytic model with a 1-year time horizon was developed from a payer's perspective in the United States (US) setting...
January 29, 2018: Journal of Medical Economics
Michael Nassif, Mikhail Kosiborod
Heart failure is one of the most common comorbidities of diabetes mellitus. Glucose-lowering therapies that can prevent heart failure or improve outcomes in patients with established heart failure are of critical importance among those with type 2 diabetes. Several types of glucose-lowering drugs have been assessed in this setting. Metformin has been shown to modestly improve the outcomes of patients with heart failure, whereas the effect of insulin in those with established heart failure is less clear. The effect of sulfonylureas on improving heart failure is controversial; observational reports have suggested that they are harmful in these patients, but these data have not been confirmed in randomized, controlled trials...
January 25, 2018: Nature Reviews. Cardiology
Cheng-Wei Chan, Chu-Leng Yu, Jiunn-Cherng Lin, Yu-Cheng Hsieh, Che-Chen Lin, Chen-Ying Hung, Cheng-Hung Li, Ying-Chieh Liao, Chu-Pin Lo, Jin-Long Huang, Ching-Heng Lin, Tsu-Juey Wu
OBJECTIVE: Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. METHODS: T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database...
January 24, 2018: Cardiovascular Diabetology
Sofie Hædersdal, Asger Lund, Filip K Knop, Tina Vilsbøll
Type 2 diabetes is a disease involving both inadequate insulin levels and increased glucagon levels. While glucagon and insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormones is awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, glucagon is equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of glucagon is essential to appreciate differences in the mechanisms of action of various classes of glucose-lowering therapies...
January 4, 2018: Mayo Clinic Proceedings
Yue Fei, Man-Fung Tsoi, Cyrus Rustam Kumana, Tommy Tsang Cheung, Bernard Man Yung Cheung
BACKGROUND: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality. METHODS: We searched MEDLINE, EMBASE, the Cochrane database, and up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients that reported MACE and deaths...
March 1, 2018: International Journal of Cardiology
Dionysis Spanopoulos, Brendan Barrett, Michael Busse, Toni Roman, Chris Poole
Members of the dipeptidyl peptidase-4 inhibitor drug class are indicated for glycemic control in patients with type 2 diabetes mellitus and all, except linagliptin, require dose adjustment in renal impairment. A cross-sectional analysis of a cohort of type 2 diabetes mellitus patients treated with dipeptidyl peptidase-4 inhibitors identified in the Clinical Practice Research Datalink was conducted to explore compliance with the renal adjustment requirements of the Summaries of Product Characteristics. Approximately one third of type 2 diabetes mellitus patients with creatinine clearance <50 mL/min who were at risk of inappropriate prescribing, were initiated on a DPP-4 inhibitor at a higher dose than the specified in their respective Summary of Product Characteristics...
January 2018: Clinical Therapeutics
Christos V Rizos, Theodosios D Filippatos, Moses S Elisaf
Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion. Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects of empagliflozin plus linagliptin combination...
December 19, 2017: Expert Opinion on Drug Metabolism & Toxicology
Giuseppe Coppolino, Christian Leporini, Laura Rivoli, Francesco Ursini, Eugenio Donato di Paola, Valeria Cernaro, Franco Arturi, Davide Bolignano, Emilio Russo, Giovambattista De Sarro, Michele Andreucci
Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non-insulin glucose-lowering agents, belonging to the incretin family, which are able to improve glycemic control with a favorable safety profile, since they are associated with a low risk of hypoglycemia, no weight gain, and good tolerability in patients with chronic renal failure. Some experimental and clinical studies suggest that these drugs may exert significant pleiotropic effects, in particular on chronic kidney disease (CKD) progression, but data from clinical trials are still controversial...
March 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jelena B Popovic-Dordevic, Ivana I Jevtic, Tatjana P Stanojkovic
BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability...
December 5, 2017: Current Medicinal Chemistry
Valentina Lorenzoni, Fabio Baccetti, Stefano Genovese, Enrico Torre, Giuseppe Turchetti
Objective: Diabetes mellitus is a chronic disease related to a significant impact in both epidemiologic and economic terms. In Italy, around 3.6 million people are affected by diabetes and this number is expected to increase significantly in the next few years. As recommended by current national and international guidelines, metformin (Met) is prescribed as first-line pharmacological treatment, and many pharmacological alternatives are available for patients uncontrolled with Met monotherapy...
2017: ClinicoEconomics and Outcomes Research: CEOR
Olga Montvida, Jonathan Shaw, John J Atherton, Frances Stringer, Sanjoy K Paul
OJBECTIVE: To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes aged 18-80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored...
November 6, 2017: Diabetes Care
G S Carls, R Tan, J Y Zhu, E Tuttle, J Yee, S V Edelman, W H Polonsky
AIMS: The study aims to examine real-world weight change and the role of medication adherence among patients with type 2 diabetes who initiated one of three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA), dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND METHODS: A cohort of patients initiating one of the three drug classes was selected from a large US database of integrated electronic medical record and administrative claims...
September 2017: Obesity Science & Practice
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
September 2017: Journal of Pharmacological Sciences
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