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Jeff Unger
Patients with type 2 diabetes (T2D) are at a greater risk of cardiovascular (CV) morbidity and mortality than their counterparts without diabetes. Worsening glycemic control is associated with increasing risk of CV events and mortality, but glycemic control alone does not appear sufficient to improve CV outcomes. Furthermore, some glucose-lowering drugs have been associated with an increased risk of CV events. As a result, the US Food and Drug Administration (FDA) issued guidance in 2008 for the investigation of CV risk with new diabetes therapies...
June 2018: Journal of Family Practice
John Anderson
Once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated improved glycemic control in patients with type 2 diabetes (T2D), and some have a number of other benefits, including weight loss, improvements in blood pressure and lipid profiles, and cardiovascular protection. They also provide a therapy option with a low risk of hypoglycemia, an attractive choice for many patients. Molecular structure and pharmacokinetic properties vary among GLP-1 RAs, with some more closely related than others to native glucagon-like peptide-1 (GLP-1)...
June 2018: Journal of Family Practice
Kuanlin Chen, Tiejun Zhuo, Jian Wang, Qing Mei
BACKGROUND AND AIMS: Saxagliptin as one of dipeptidyl peptidase-4 (DPP-4) inhibitors can effectively improve glycaemic control in type 2 diabetes mellitus, and nesfatin-1 is regarded as a very important factor in regulating feeding behavior and energy homeostasis. In this trial, we observed the effect of saxagliptin on regulating nesfatin-1 secretion and ameliorating insulin resistance and metabolic profiles in type 2 diabetes mellitus. METHODS: One hundred two type 2 diabetes participants (M/F = 48/54) were investigated...
June 18, 2018: Metabolic Syndrome and related Disorders
Olufunto O Badmus, Lawrence A Olatunji
OBJECTIVE: We tested the hypothesis that glucocorticoid (GC) exposure in female rats would lead to glucose dysregulation and elevated cardiac inflammatory biomarkers, which are dipeptidyl peptidase-4 (DPP-4)- and glycogen synthase kinase-3 (GSK-3)-dependent. METHODS: Female Wistar rats received vehicle (control; n = 6) or GC (dexamethasone; n = 6; 0.2 mg/kg; p.o.) for six days. Insulin resistance was determined by HOMA-IR. DPP-4 activity was determined by fluorescence method, whereas vascular cell adhesion molecule-1 (VCAM-1), uric acid, malondialdehyde (MDA), lactate dehydrogenase (LDH) and nitric oxide (NO) from plasma and cardiac homogenate were estimated as cardiac pro-inflammatory biomarkers...
June 18, 2018: Archives of Physiology and Biochemistry
Bassam M Ayoub, Shereen Mowaka, Marwa M Safar, Nermeen Ashoush, Mona G Arafa, Haidy E Michel, Mariam M Tadros, Mohamed M Elmazar, Shaker A Mousa
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work...
June 12, 2018: Scientific Reports
Bradley S Fleenor, An Ouyang, T Dylan Olver, Jessica A Hiemstra, Melissa S Cobb, Gianmaria Minervini, Craig A Emter
Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine...
June 11, 2018: Hypertension
Poonam Kalhotra, Veera C S R Chittepu, Guillermo Osorio-Revilla, Tzayhri Gallardo-Velázquez
Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer...
June 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Weijia Xie, Xiaoxiao Song, Zhenjie Liu
Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications...
June 4, 2018: Vascular Pharmacology
Ankit Rohilla, Tanya Gupta, Ankita Pathak, Md J Akhtar, Md R Haider, Kashif Haider, Mohammad Shahar Yar
Diabetes has turned out to be an epidemic in the recent years all over the world, and today it has become a burden on the healthcare system. Over the years, with technological advancements, different classes of antidiabetic medications have emerged, like sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones, but these are often loaded with serious aftermaths like hypoglycemia, weight gain, cardiovascular and renal issues. Dipeptidyl peptidase-4 (DPP-4) inhibition is an exciting and new approach in the treatment of type-2 diabetes...
June 7, 2018: Archiv der Pharmazie
Helena W Rodbard
GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time...
June 5, 2018: Diabetes Technology & Therapeutics
Gian Paolo Fadini, Daniele Bottigliengo, Federica D'Angelo, Franco Cavalot, Antonio Carlo Bossi, Giancarlo Zatti, Ileana Baldi, Angelo Avogaro
INTRODUCTION: DPP-4 inhibitors (DPP4i) and sulfonylureas are popular second-line therapies for type 2 diabetes (T2D), but there is a paucity of real-world studies comparing their effectiveness in routine clinical practice. METHODS: This was a multicenter retrospective study on diabetes outpatient clinics comparing the effectiveness of DPP4i versus gliclazide extended release. The primary endpoint was change from baseline in HbA1c. Secondary endpoints were changes in fasting plasma glucose, body weight, and systolic blood pressure...
June 1, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Juan Ling, Long Ge, Ding-Hua Zhang, Yong-Feng Wang, Zhuo-Lin Xie, Jin-Hui Tian, Xiao-Hui Xiao, Ke-Hu Yang
AIMS: To evaluate the methodological quality of systematic reviews (SRs), and summarize evidence of important outcomes from dipeptidyl peptidase-4 inhibitors (DPP4-I) in treating type 2 diabetes mellitus (T2DM). METHODS: We included SRs of DPP4-I for the treatment of T2DM until January, 2018 by searching the Cochrane Library, PubMed, EMBASE and three Chinese databases. We evaluated the methodological qualities with the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool and the GRADE (The Grading of Recommendations Assessment, Development and Evaluation) approach...
June 1, 2018: Acta Diabetologica
Bruce C Stuart, Julia F Slejko, Juan-David Rueda, Catherine Cooke, Xian Shen, Pamela Roberto, Michael Ciarametaro, Robert Dubois
OBJECTIVES: To explore formulary restrictions on noninsulin antihyperglycemic drugs (NIADs) in Medicare Part D plans and to estimate the impact of formulary restrictions on use of NIADs among low-income subsidy (LIS) recipient enrollees with type 2 diabetes (T2D) undergoing treatment intensification. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort of 2919 LIS enrollees with T2D receiving metformin monotherapy during the first quarter of 2012 who intensified treatment later in the year was tracked to assess selection of and days' supply with sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and other NIADs...
May 2018: American Journal of Managed Care
Takuya Imatoh, Takumi Nishi, Midori Yasui, Toshiki Maeda, Kimie Sai, Yoshiro Saito, Hiroshi Une, Akira Babazono
PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients. METHODS: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016...
May 30, 2018: Pharmacoepidemiology and Drug Safety
R Stenlid, H Manell, M Halldin, J Kullberg, H Ahlström, L Manukyan, D Weghuber, K Paulmichl, F Zsoldos, P Bergsten, A Forslund
Context: Dipeptidyl Peptidase-4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1) and increased DPP4 levels are associated with obesity and visceral adiposity in adults. Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments. Design: Cross-sectional study, July 2012 to April 2015...
May 29, 2018: Journal of Clinical Endocrinology and Metabolism
Petr Jarolim, William B White, Christopher P Cannon, Qi Gao, David A Morrow
OBJECTIVE: Patients with type 2 diabetes are at increased risk of developing heart failure (HF). Enhanced recognition of patients at risk for HF would help guide therapeutic decisions. RESEARCH DESIGN AND METHODS: We investigated the prognostic implications of changes in N-terminal B-type natriuretic peptide (NT-proBNP) concentration in patients with type 2 diabetes and ischemic heart disease who were enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial, a phase 3b trial of alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor...
May 30, 2018: Diabetes Care
W Ryan Powell, Cindy L Christiansen, Donald R Miller
INTRODUCTION: Among the most pressing clinical decisions in type 2 diabetes treatments are which drugs should be used after metformin is no longer sufficient, and whether sulfonylureas (SUs) should remain as a suitable second-line treatment. In this article we summarize current evidence on the long-term safety risks associated with SU therapy relative to other oral glucose-lowering therapies. METHODS: The MEDLINE database and were searched for observational and experimental studies comparing the safety of SUs to that of other diabetes medications in people with type 2 diabetes mellitus through December 15, 2015...
May 28, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Ulf Elbelt
Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated...
June 2018: Deutsche Medizinische Wochenschrift
Yunyi Gao, Yujie Liang, Xingwu Ran
Objective: To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. Methods: The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. Results: DPP-4 inhibitors can accelerated the ulcer healing...
May 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
Katarina Tomovic, Jelena Lazarevic, Gordana Kocic, Marina Deljanin-Ilic, Marko Anderluh, Andrija Smelcerovic
Dipeptidyl peptidase-4 (DPP-4) cleaves N-terminal dipeptides, with Pro, Ala or Ser at the penultimate position, and, in that way, modulates biological activity of certain polypeptides. Due to its ubiquitous distribution, many pathological processes are associated with altered DPP-4 expression and activity. Besides the regulation of glucose metabolism, DPP-4 also exhibits many other systemic effects, and the inhibition of its activity might lead to cardiovascular and renal protection. Mechanisms underlying these protective effects of DPP-4 inhibition are ascribed to elevated bioavailability of its substrates, to impacts on mediators and signaling pathways that ameliorate cardiovascular and renal function through the suppression of oxidative stress, inflammation, fibrosis and apoptosis, improved endothelial function and tissue reparation...
May 28, 2018: Medicinal Research Reviews
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