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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/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#4
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/29623219/management-strategies-for-posttransplant-diabetes-mellitus-after-heart-transplantation-a-review
#5
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/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
#6
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/29601817/glp-1-receptor-agonist-liraglutide-exerts-central-action-to-induce-%C3%AE-cell-proliferation-through-medulla-to-vagal-pathway-in-mice
#7
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
#8
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/29579035/diabetes-and-cardiovascular-disease-from-new-mechanisms-to-new-therapies
#9
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
#10
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/29561188/short-term-sitagliptin-metformin-therapy-is-more-effective-than-metformin-or-placebo-in-prior-gestational-diabetic-women-with-impaired-glucose-regulation
#11
Karen E Elkind-Hirsch, Martha S Paterson, Donna Shaler, Hanh C Gutowski
OBJECTIVE: Our pilot study examined the effectiveness of sitagliptin-metformin (SITA-MET), metformin (MET), and placebo (P) therapy on fasting and post-glucose challenge glucose levels in postpartum women with prior gestational diabetes mellitus (GDM) and impaired glucose regulation. METHODS: Prediabetic women (N = 36, age 18 to 42 years) with recent GDM were randomized to P (one pill twice a day), MET (1,000 mg twice a day), or SITA-MET (50 mg SITA, 1,000 mg MET twice a day) for 16 weeks in a single-blind fashion...
March 21, 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29553076/-type-2-diabetes-and-vascular-endothelial-dysfunction
#12
Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions...
2018: Journal of UOEH
https://www.readbyqxmd.com/read/29536608/long-term-sustainability-of-glycaemic-achievements-with-second-line-anti-diabetic-therapies-in-patients-with-type-2-diabetes-a-real-world-study
#13
Olga Montvida, Jonathan Shaw, Lawrence Blonde, Sanjoy K Paul
AIMS: To inform patients and their carers about the probability of reducing HbA1c to clinically desirable levels and sustainability of such control over 2 years with major second-line anti-diabetic therapies under individual risk scenario, with and without third-line intensification. MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163,081 patients with type 2 diabetes aged 18-80 years, who initiated metformin; intensified with DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, insulin, or thiazolidinedione; and continued second-line ≥ 6 month, were selected...
March 14, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29522713/replacement-of-the-c-terminal-trp-cage-of-exendin-4-with-a-fatty-acid-improves-therapeutic-utility
#14
Jung Gi Lee, Jae Ha Ryu, Seon-Myung Kim, Moon-Young Park, San-Ho Kim, Young G Shin, Jong-Woo Sohn, Ha Hyung Kim, Zee-Yong Park, Jae Young Seong, Jae Il Kim
Exendin-4, a 39 amino acid peptide isolated from the saliva of the Gila monster, plays an important role in regulating glucose homeostasis, and is used clinically for the treatment of type 2 diabetes. Exendin-4 shares 53% sequence identity with the incretin hormone glucagon-like peptide 1 (GLP-1) but, unlike GLP-1, is highly resistant to proteolytic enzymes such as dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase 24.11 (NEP 24.11). Herein, we focused on the structure and function of the C-terminal Trp-cage of exendin-4, and suggest that it may be structurally required for resistance to proteolysis by NEP 24...
March 6, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29516618/sodium-glucose-co-transporter-2-inhibitors-sglt2is-the-latest-residents-on-the-block-impact-on-glycaemic-control-at-a-general-practice-level-in-england
#15
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29516612/use-and-effectiveness-of-dapagliflozin-in-routine-clinical-practice-an-italian-multicenter-retrospective-study
#16
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination...
March 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29511780/evaluation-of-pharmacokinetic-and-pharmacodynamic-parameters-following-single-dose-of-sitagliptin-in-healthy-indian-males
#17
Ganesh V Sangle, Mohan Patil, Nitin J Deshmukh, Sushant A Shengule, Shantibhushan Kamble, Kiran Kumar Vuppalavanchu, Sushil Kale, Mirza Layeeq Ahmed Baig, Geetchandra Singh, Javed Shaikh, Jitendra Tripathi, P Aravindababu
PURPOSE: Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagliptin 100 mg (Januvia) in healthy Indian male participants. METHOD: In a randomised, single-dose, open-label, three-treatment, three-period, three-sequence, crossover bioavailability study, 18 healthy male participants received single-dose of sitagliptin under fasted and fed conditions...
March 6, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29507662/teneligliptin-enhances-the-beneficial-effects-of-glp-1-in-endothelial-cells-exposed-to-hyperglycemic-conditions
#18
Valeria De Nigris, Francesco Prattichizzo, Elettra Mancuso, Rosangela Spiga, Gemma Pujadas, Antonio Ceriello
High-glucose-induced oxidative stress contributes to cardiovascular endothelial damage in diabetes. Glucagon-like peptide 1 (GLP-1) is beneficial to endothelial cells, but its effects are diminished when cells are continuously exposed to high glucose. Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that prevents oxidative stress, apoptosis and the metabolic memory effect. We explored the potential additive effects of Teneligliptin and GLP-1 in hyperglycemia-damaged endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed to normal-glucose (5 mmol/L) or high-glucose (HG, 25 mmol/L) for 21 days, or to HG for 14 days followed by normal-glucose for 7 days (HM)...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29498469/different-glucagon-effects-during-dpp-4-inhibition-versus-sglt-2-inhibition-in-metformin-treated-type-2-diabetes-subjects
#19
Wathik Alsalim, Margaretha Persson, Bo Ahrén
AIMS: Previous studies have shown that dipeptidyl peptidase (DPP)-4 inhibition lowers whereas sodium-glucose co-transporter 2 (SGLT-2) inhibition increases glucagon levels. This study evaluated the extent of these opposite effects in a direct comparative head-to-head study. METHODS: In a single-centre, randomized study with a cross-over design, 28 metformin-treated patients with type 2 diabetes (T2D; mean age 63 years, baseline HbA1c 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for two weeks with a four week wash out period in between...
March 2, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29495245/yh18968-a-novel-1-2-4-triazolone-g-protein-coupled-receptor-119-agonist-for-the-treatment-of-type-2-diabetes-mellitus
#20
Taedong Han, Byoung Moon Lee, Yoo Hoi Park, Dong Hoon Lee, Hyun Ho Choi, Taehoon Lee, Hakwon Kim
G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay...
March 1, 2018: Biomolecules & Therapeutics
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