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https://www.readbyqxmd.com/read/28640857/glucose-dysregulation-and-response-to-common-anti-diabetic-agents-in-the-fatzo-pco-mouse
#1
Richard G Peterson, Charles Van Jackson, Karen M Zimmerman, Jorge Alsina-Fernandez, M Dodson Michael, Paul J Emmerson, Tamer Coskun
The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances...
2017: PloS One
https://www.readbyqxmd.com/read/28606343/pharmacologic-management-of-type-2-diabetes-mellitus-available-therapies
#2
James Thrasher
Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28606340/cardiovascular-protection-in-the-treatment-of-type-2-diabetes-a%C3%A2-review-of-clinical-trial-results-across-drug-classes
#3
Francesco Paneni, Thomas F Lüscher
Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28572879/effects-of-glycaemic-management-on-diabetic-kidney-disease
#4
REVIEW
Richard J MacIsaac, George Jerums, Elif I Ekinci
Hyperglycaemia contributes to the onset and progression of diabetic kidney disease (DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro- or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient...
May 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28569363/glucagon-like-peptide-1-receptor-agonists-and-atrial-fibrillation-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#5
M Monami, B Nreu, A Scatena, S Giannini, F Andreozzi, G Sesti, E Mannucci
BACKGROUND: The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation. METHODS: A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug...
May 31, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28550608/shifting-paradigms-in-the-medical-management-of-type-2-diabetes-reflections-on-recent-cardiovascular-outcome-trials
#6
Faramarz Ismail-Beigi, Etie Moghissi, Mikhail Kosiborod, Silvio E Inzucchi
An important challenge in the management of patients with type 2 diabetes is cardiovascular disease (CVD) prevention. While it is well established that intensive glycemic control prevents the onset and slows the progression of certain microvascular complications, such a strategy utilized in multiple clinical trials over the past few decades has failed to show a similar benefit with regard to cardiovascular events, including mortality. Despite this, a major hope has been the discovery of glucose-lowering medications that simultaneously improve cardiovascular outcomes...
May 26, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28545639/novel-diabetes-drugs-and-the-cardiovascular-specialist
#7
REVIEW
Naveed Sattar, Mark C Petrie, Bernard Zinman, James L Januzzi
Recently, treatment with 2 newer classes of type 2 diabetes drugs were found to reduce events in patients with diabetes and cardiovascular (CV) disease, a group common in cardiology clinics. The sodium-glucose cotransporter 2 inhibitor, empagliflozin, markedly and rapidly reduced CV death and heart failure hospitalization, likely with hemodynamic/metabolic-driven mechanisms of action. More recently, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide also reduced CV death and/or major adverse CV events, but did so more slowly and did not influence heart failure risks, suggesting alternative mechanisms of benefit...
May 30, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28537000/advances-in-clinical-cardiology-2016-a-summary-of-the-key-clinical-trials
#8
REVIEW
Alastair Gray, Conor McQuillan, Ian B A Menown
INTRODUCTION: The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. METHODS: The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA)...
May 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#9
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28526920/effects-of-semaglutide-on-beta-cell-function-and-glycaemic-control-in-participants-with-type-2-diabetes-a-randomised-double-blind-placebo-controlled-trial
#10
Christoph Kapitza, Kirsten Dahl, Jacob B Jacobsen, Mads B Axelsen, Anne Flint
AIMS/HYPOTHESIS: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed. METHODS: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA1c of 6...
May 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526186/cardiovascular-protection-in-the-treatment-of-type-2-diabetes-a-review-of-clinical-trial-results-across-drug-classes
#11
Francesco Paneni, Thomas F Lüscher
Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526182/pharmacologic-management-of-type-2-diabetes-mellitus-available-therapies
#12
James Thrasher
Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin...
May 12, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28514822/-cardiovascular-effects-of-antidiabetic-therapies
#13
Katharina Laubner, Jochen Seufert
Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin...
May 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28501352/effects-of-glucagon-like-peptide-1-receptor-agonists-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#14
Matteo Monami, Stefania Zannoni, Laura Pala, Antonio Silverii, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials suggested a possible beneficial effect of the class of GLP-1 receptor agonists on cardiovascular morbidity and mortality. The aim of the present meta-analysis is to collect and synthetize all available evidence on the effect of GLP-1 receptor agonists on cardiovascular events and mortality. METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug...
August 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28483748/cardiovascular-safety-outcomes-of-new-antidiabetic-therapies
#15
Marlys H LeBras, Arden R Barry, Sheri L Koshman
PURPOSE: The cardiovascular safety outcomes of newer antidiabetic agents were reviewed. SUMMARY: Seven randomized, placebo-controlled trials involving patients with type 2 diabetes mellitus with or at risk for cardiovascular disease were reviewed. The trials examined the cardiovascular safety outcomes of the following agents: alogliptin, saxagliptin, and sitagliptin (dipeptidyl peptidase-4 [DPP-4] inhibitors); liraglutide, lixisenatide, and semaglutide (glucagon-like peptide-1 agonists); and empagliflozin (a sodium glucose cotransport-2 inhibitor)...
May 8, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28431669/after-the-leader-trial-and-sustain-6-how-do-we-explain-the-cardiovascular-benefits-of-some-glp-1-receptor-agonists
#16
B Vergès, B Charbonnel
Recent cardiovascular outcome trials - the LEADER with liragutide and SUSTAIN-6 with semaglutide - have shown significant reductions of major cardiovascular (CV) events with these glucagon-like peptide (GLP)-1 receptor agonists. Progressive separation of the treatment and placebo curves, starting clearly between 12 and 18 months of the trial period, and significant reductions in the risk of myocardial infarction and stroke, indicate that the beneficial CV effects observed with GLP-1 receptor agonists could be due to an antiatherogenic effect...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#17
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28413990/effect-of-glucagon-like-peptide-1-receptor-agonists-on-all-cause-mortality-and-cardiovascular-outcomes-a-meta-analysis
#18
Shaylee Peterson, Arden Barry
BACKGROUND: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. OBJECTIVE: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes. METHOD: EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes...
April 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#19
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
May 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28392300/glucagon-like-peptide-1-receptor-agonists-a-class-update-for-treating-type-2-diabetes
#20
REVIEW
Julie A Lovshin
Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia...
April 5, 2017: Canadian Journal of Diabetes
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