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https://www.readbyqxmd.com/read/29667921/glycemic-control-of-type-2-diabetes-mellitus-across-stages-of-renal-impairment-information-for-primary-care-providers
#1
Lili Tong, Sharon Adler
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications...
April 18, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#2
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29655980/evaluation-of-novel-tgr5-agonist-in-combination-with-sitagliptin-for-possible-treatment-of-type-2-diabetes
#3
Sameer Agarwal, Santosh Sasane, Jeevan Kumar, Prashant Deshmukh, Hitesh Bhayani, Poonam Giri, Suresh Giri, Shubhangi Soman, Neelima Kulkarni, Mukul Jain
TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes...
April 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29655978/sitagliptin-prevents-isoproterenol-induced-myocardial-infarction-in-rats-by-modulating-nitric-oxide-synthase-enzymes
#4
Mohamed Abdellah Ibrahim, Ayman Geddawy, Soha Abdel-Wahab
Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The study investigated the ability of sitagliptin to prevent pathological changes of isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide (NO) was also reported. Rats were assorted into six groups (n = 7) and treated for 12 days. Group 1: normal control, received normal saline. Group 2, sitagliptin control, received sitagliptin (10mg/kg, orally)...
April 12, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#5
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29645341/effects-on-the-glucagon-response-to-hypoglycaemia-during-dpp-4-inhibition-in-elderly-subjects-with-type-2-diabetes-a-randomized-placebo-controlled-study
#6
Johan Farngren, Margaretha Persson, Bo Ahrén
AIMS: Maintained glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study. METHODS: In a single-center, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 males, 11 females; mean 74 years (range 65-86 years), mean HbA1c 51...
April 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29623219/management-strategies-for-posttransplant-diabetes-mellitus-after-heart-transplantation-a-review
#7
REVIEW
Matthew G Cehic, Nishant Nundall, Jerry R Greenfield, Peter S Macdonald
Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation...
2018: Journal of Transplantation
https://www.readbyqxmd.com/read/29609120/recent-progress-of-the-development-of-dipeptidyl-peptidase-4-inhibitors-for-the-treatment-of-type-2-diabetes-mellitus
#8
Ning Li, Li-Jun Wang, Bo Jiang, Xiang-Qian Li, Chuan-Long Guo, Shu-Ju Guo, Da-Yong Shi
Diabetes is a fast growing chronic metabolic disorder around the world. Dipeptidyl peptidase-4 (DPP-4) is a new promising target during type 2 diabetes glycemic control. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. This article reviews the development of synthetic and natural DPP-4 inhibitors from 2012 to 2017 and provides their physico-chemical properties, biological activities against DPP-4 and selectivity over dipeptidyl peptidase-8/9...
March 21, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29607314/glucagon-like-peptide-1-mediates-the-protective-effect-of-the-dipeptidyl-peptidase-iv-inhibitor-on-renal-fibrosis-via-reducing-the-phenotypic-conversion-of-renal-microvascular-cells-in-monocrotaline-treated-rats
#9
Jian Xu, Jingjing Wang, Yusheng Cheng, Xiang Li, Mengyu He, Jiali Zhu, Honghao Han, Guihong Wei, Hui Kong, Weiping Xie, Hong Wang, Xiangrong Zuo
Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29605771/the-dipeptidyl-peptidase-4-dpp-4-inhibitor-sitagliptin-ameliorates-retinal-endothelial-cell-dysfunction-triggered-by-inflammation
#10
Andreia Gonçalves, Luísa Almeida, Ana Paula Silva, Carlos Fontes-Ribeiro, António F Ambrósio, Armando Cristóvão, Rosa Fernandes
Diabetic retinopathy is considered a low-grade chronic inflammatory disease and several inflammatory molecules, including tumor necrosis factor (TNF)-α, are known to play a major role in the degeneration of retinal capillaries. Previous studies have reported that sitagliptin, a DPP-4 inhibitor, prevents the increase in blood-retinal barrier (BRB) permeability and inhibits the tight junction disassembly induced by diabetes. AIM: Our goal was to investigate whether sitagliptin is able to prevent retinal endothelial cells (EC) dysfunction triggered by the pro-inflammatory cytokine TNF-α...
March 29, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29605417/linagliptin-attenuates-chronic-post-ischemia-pain-possible-anti-inflammatory-and-anti-oxidant-mechanisms
#11
Wafaa A Hewedy
Complex regional pain syndrome (CRPS) is a debilitating neurologic disorder with an interlinked and yet incompletely defined pathogenesis. Treatment options remain a therapeutic challenge. Linagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors which are used for the treatment of diabetes mellitus. Apart from the improvement of glycemic control, accumulating evidence points to the beneficial effects of DPP-4 inhibitors in a wide array of conditions. Herein, the present study was outlined to investigate the antinociceptive effect of linagliptin in acute pain conditions, and in an animal model of CRPS...
March 29, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29601817/glp-1-receptor-agonist-liraglutide-exerts-central-action-to-induce-%C3%AE-cell-proliferation-through-medulla-to-vagal-pathway-in-mice
#12
Parmila Kumari, Masanori Nakata, Bo Yang Zhang, Zesemdorj Otgon-Uul, Toshihiko Yada
Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are administered at 10 times higher concentration than endogenous GLP-1 level, which enables them to reach several brain regions including ARC and AP, the areas implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed clinically and experimentally, including pancreatic β-cell proliferation, are thought to involve the brain...
March 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29600430/targeting-incretin-hormones-and-the-ask-1-pathway-as-therapeutic-options-in-the-treatment-of-non-alcoholic-steatohepatitis
#13
REVIEW
Alexander J Kovalic, Sanjaya K Satapathy, Naga Chalasani
Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms of chronic liver disease, and its rising frequency worldwide has reached epidemic proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex, and as such myriad therapies are under investigation targeting different pathophysiological mechanisms...
March 29, 2018: Hepatology International
https://www.readbyqxmd.com/read/29596951/a-randomized-controlled-trial-to-compare-the-effects-of-sulphonylurea-gliclazide-mr-modified-release-and-the-dpp-4-inhibitor-vildagliptin-on-glycemic-variability-and-control-measured-by-continuous-glucose-monitoring-cgm-in-brazilian-women-with-type-2-diabetes
#14
Andre Gustavo Daher Vianna, Claudio Silva Lacerda, Luciana Muniz Pechmann, Michelle Garcia Polesel, Emerson Cestari Marino, Jose Rocha Faria-Neto
AIMS: This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). METHODS: An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60 to 120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks...
March 26, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29581078/alogliptin-in-patients-with-type-2-diabetes-on-metformin-and-sulfonylurea-therapies-in-the-examine-trial
#15
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/29579035/diabetes-and-cardiovascular-disease-from-new-mechanisms-to-new-therapies
#16
Grzegorz Gajos
Diabetes increases the risk of cardiovascular diseases, which are the leading cause of mortality among diabetic patients. Although hyperglycemia is a major determinant of macrovascular and microvascular complications in diabetes, hypoglycemia and glycemic variability have also a strong influence on the cardiovascular system. This overview presents the current state of knowledge on the impact of type 2 diabetes on the cardiovascular system and new therapeutic strategies that have been recently developed to correct gluco-metabolic disturbances in patients with high cardiovascular risk, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors...
March 29, 2018: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29577365/oleuropein-a-component-of-extra-virgin-olive-oil-lowers-post-prandial-glycaemia-in-healthy-subjects
#17
Roberto Carnevale, Romano Silvestri, Lorenzo Loffredo, Marta Novo, Vittoria Cammisotto, Valentina Castellani, Simona Bartimoccia, Cristina Nocella, Francesco Violi
AIMS: Extra virgin olive oil (EVOO) lowers post-prandial glycaemia. We investigated if oleuropein, a component of EVOO, exerts a similar effect on post-prandial glycaemia and the underlying mechanism. METHODS: Twenty healthy subjects were randomly allocated in a cross-over design to 20 mg oleuropein or placebo immediately before lunch. Post-prandial glycaemia along with blood insulin, dipeptidyl-peptidase-4 (DPP-4) and glucagon-like peptide-1 (GLP-1) and oxidative stress, which included Nox2 activity(sNox2-dp), 8-iso-PGF2α and platelet p47phox phosphorylation, were analysed before and two hours after meal...
March 26, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29573125/risk-of-dipeptidyl-peptidase-4-dpp-4-inhibitors-on-site-specific-cancer-a-systematic-review-and-meta-analysis
#18
REVIEW
Jetty A Overbeek, Marina Bakker, Amber A W A van der Heijden, Myrthe P P van Herk-Sukel, Ron M C Herings, Giel Nijpels
BACKGROUND: The long-term impact of DPP-4 inhibition is unknown and there are concerns about the influence of DPP-4 inhibition on carcinogenesis of the pancreas and thyroid. As DPP-4 is a rather unselective enzyme present in many tissues, we focused on all specific cancer types. METHODS: PubMed and EMBASE were searched between Jan 2005 and Apr 2017 to identify studies comparing DPP-4 inhibitors with either placebo or active drugs on cancer risk. Studies were included if they reported on at least one specific cancer outcome and had a follow-up of at least one year after start of drug use...
March 23, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29573110/sglt2-inhibitor-plus-dpp-4-inhibitor-as-combination-therapy-for-type-2-diabetes-a-systematic-review-and-meta-analysis
#19
Dandan Li, Weilong Shi, Tiansheng Wang, Huilin Tang
To assess the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors plus dipeptidyl peptidase-4 (DPP-4) inhibitor in patients with type 2 diabetes mellitus (T2DM), we performed a systematic review and meta-analysis of 14 randomized controlled trials (RCTs) involving 4,828 patients. Compared with DPP-4 inhibitor, SGLT2 inhibitor/DPP-4 inhibitor combination therapy was significantly associated with a decrease in glycemic control [HbA1c: -0.71%, fasting plasma glucose (FPG): -25.62 mg/dL, postprandial plasma glucose: -44...
March 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29569809/commentary-on-changing-prevalence-of-diabetes-mellitus-in-bullous-pemphigoid-it-is-the-dipeptidyl-peptidase-4-inhibitors
#20
L Fania, G Di Zenzo, C Mazzanti, D Abeni
In their article entitled "Changing prevalence of diabetes mellitus in bullous pemphigoid: It is the dipeptidyl peptidase-4 inhibitors" Gravani and colleagues1 confirmed the increasing incidence of bullous pemphigoid (BP) in the last decade, and highlighted its association with diabetes mellitus (DM), and specifically with dipeptidyl peptidase-4 inhibitors (DPP-4-i). As the Authors noted, these data expand the results of our study2 , in which we underscored, collecting administrative data from our Institute during the years 2001-2016 and studying the prevalence of diabetes in patients with pemphigus and BP, the higher frequency of DM in BP patients during the last decade...
March 23, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
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