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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/29024408/effects-of-glucagon-like-peptide-1-glp-1-receptor-agonists-on-cardiovascular-risk-factors-a-narrative-review-of-head-to-head-comparisons
#1
REVIEW
Niels B Dalsgaard, Tina Vilsbøll, Filip K Knop
Cardiovascular (CV) disease is the leading cause of death and morbidity in patients with type 2 diabetes. Five CV risk factors (blood pressure, resting heart rate [HR], body weight, cholesterol levels and blood glucose) are monitored routinely as safety and efficacy endpoints in randomised clinical trials for diabetes therapies. To determine if different glucagon-like peptide-1 receptor agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16 head-to-head trials directly comparing GLP-1RAs that included at least one of the five factors...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29024310/influence-of-metabolic-syndrome-and-race-on-the-relationship-between-intensive-blood-pressure-control-and-cardiovascular-outcomes-in-the-sprint-cohort
#2
Kathleen Dungan, Timothy E Craven, Kyaw Soe, Jackson T Wright, Jan Basile, William E Haley, Nancy R Kressin, Uzma Rani, Leonardo Tamariz, Jeff Whittle, Alan Wiggers, Kwame Osei
AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether effects varied by race/ethnicity. MATERIALS AND METHODS: We performed post-hoc analyses among Non-Hispanic Black (NHB), Non-Hispanic White (NHW), and Hispanic participants with and without MetS in the Systolic Blood Pressure Intervention Trial (SPRINT) randomized to a systolic blood pressure (SBP) target of less than 120 mm Hg (intensive group, N = 4544) or one less than 140 mm Hg (standard group, N = 4553)...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29024278/why-do-sglt2-inhibitors-reduce-heart-failure-hospitalization-a-differential-volume-regulation-hypothesis
#3
REVIEW
K Melissa Hallow, Gabriel Helmlinger, Peter J Greasley, John J V McMurray, David W Boulton
The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28967181/metformin-and-beta-cell-function-in-insulin-treated-patients-with-type-2-diabetes-a-randomized-placebo-controlled-4-3-year-trial
#4
Wiebe Top, Coen Stehouwer, Philippe Lehert, Adriaan Kooy
Metformin is a key drug in the treatment of type 2 diabetes. In our 'Hyperinsulinaemia: the Outcome of its Metabolic Effects (HOME) Study' we showed that metformin vs placebo improved glycemic control and decreased insulin requirements in insulin-treated patients with advanced type 2 diabetes (1).
October 2, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28950422/liraglutide-and-cardiovascular-outcomes-in-adults-with-overweight-or-obesity-a-post-hoc-analysis-from-scale-randomized-controlled-trials
#5
M J Davies, L J Aronne, I D Caterson, A B Thomsen, P B Jacobsen, S P Marso
The cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist approved for weight management at a dose of 3.0 mg, was evaluated post hoc using data from 5908 participants in 5 randomized, double-blind, placebo-controlled clinical trials. Participants were randomized to liraglutide or a comparator group (placebo or orlistat). The objective was to evaluate whether cardiovascular risk was increased with liraglutide treatment. The primary composite outcome of this time-to-event analysis was the first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke...
September 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28950419/dapagliflozin-in-patients-with-type-2-diabetes-mellitus-a-pooled-analysis-of-safety-data-from-phase-2b-3-clinical-trials
#6
Serge Jabbour, Jochen Seufert, Andre Scheen, Clifford J Bailey, Cathrina Karup, Anna Maria Langkilde
AIM: Dapagliflozin is a highly selective sodium-glucose cotransporter-2 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). This pooled analysis evaluated the safety and tolerability of dapagliflozin in patients with T2DM. METHODS: Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n=2360; placebo, n=2295). Larger placebo/comparator-controlled pools of 21 (≤208 week; dapagliflozin, n=5936; control, n=3403) and 30 trials (≥12 week; dapagliflozin, n=9195; control, n=4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower-limb amputation, respectively...
September 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28950045/non-st-elevation-myocardial-infarction-nstemi-outcome-in-type-2-diabetic-patients-with-non-obstructive-coronary-artery-stenosis-effects-of-incretin-treatment
#7
Raffaele Marfella, Celestino Sardu, Paolo Calabrò, Mario Siniscalchi, Fabio Minicucci, Giuseppe Signoriello, Maria Luisa Balestrieri, Ciro Mauro, Maria Rosaria Rizzo, Giuseppe Paolisso, Michelangela Barbieri
No proper data on prognosis and management of type-2 diabetic patients with non-obstructive coronary artery stenosis (NOCS)-Non-ST-Elevation Myocardial Infarction (NSTEMI) exist. We evaluated the 12-months prognosis of NOCS-diabetics (20-49% luminal stenosis) with first NSTEMI as compared with non-diabetics. Moreover, we investigated the 12-months prognosis in NSTEMI-NOCS diabetics, previously treated with incretin-based therapy, compared with a matched cohort of NSTEMI-NOCS never treated with such therapy...
September 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28941314/semaglutide-improves-postprandial-glucose-and-lipid-metabolism-and-delays-first-hour-gastric-emptying-in-subjects-with-obesity
#8
J B Hjerpsted, A Flint, A Brooks, M B Axelsen, T Kvist, J Blundell
AIM: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. MATERIALS AND METHODS: This was a randomised, double-blind, placebo-controlled, two-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardised meals...
September 23, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28941313/different-intervention-strategies-for-preventing-type-2-diabetes-mellitus-in-china-a-systematic-review-and-network-meta-analysis-of-randomized-controlled-trials
#9
Bing Pang, Lin-Hua Zhao, Xin-Long Li, Jun Song, Qing-Wei Li, Xing Liao, Shuo Feng, Xi-Yan Zhao, Yu-Jiao Zheng, Xiao-Wen Gou, Qing Ni, Xiao-Lin Tong
Different strategies are increasingly used for early intervention on prediabetes in China, but the effects of these strategies on incident diabetes have not yet been confirmed. This study was to systematically assess the effects of different strategies on preventing diabetes, aimed at Chinese prediabetic subjects. Seven electronic databases were searched to identify eligible trials published from inception to Sep 20, 2016. Randomized controlled trials with a minimum follow-up duration of 6 months were included...
September 23, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28940946/islet-neuropeptide-y-receptors-are-functionally-conserved-and-novel-targets-for-the-preservation-of-beta-cell-mass
#10
Z J Franklin, A Tsakmaki, P Fonseca Pedro, A J King, G C Huang, S J Persaud, G A Bewick
OBJECTIVE: Two unmet therapeutic strategies for diabetes treatment are prevention of beta-cell death and stimulation of beta-cell replication. Our aim was to characterise the role of Neuropeptide Y receptors in the control of beta-cell mass. METHODS: We used endogenous and selective agonists of the NPY receptor system to explore its role in the prevention of beta-cell apoptosis and proliferation in islets isolated from both mouse and human donors. We further explored the intra-cellular signalling cascades involved using chemical inhibitors of key signalling pathways...
September 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28940961/perioperative-continuation-of-metformin-does-not-improve-glycemic-control-in-patients-with-type-2-diabetes-a-randomized-controlled-trial
#11
A H Hulst, J A W Polderman, E Ouweneel, A J Pijl, M W Hollmann, J H DeVries, B Preckel, J Hermanides
Historically, metformin was withheld before surgery in fear of metformin associated lactic acidosis. Now, this risk is deemed low and guidelines move towards continuation of metformin. We hypothesized that continuing metformin perioperatively would lower postoperative serum glucose without an effect on plasma lactate. We performed a single-blind multicenter RCT in type 2 diabetes mellitus patients scheduled for non-cardiac surgery and continued (MF+) or withheld (MF-) metformin before surgery. Main outcome parameters were the differences in perioperative plasma glucose and lactate levels...
September 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28926170/efficacy-and-safety-of-saxagliptin-in-combination-with-metformin-as-initial-therapy-in-chinese-patients-with-type-2-diabetes-results-from-the-start-study-a-multicenter-randomized-double-blind-active-controlled-phase-3-trial
#12
Jingtao Dou, Jianhua Ma, Jun Liu, Changjiang Wang, Eva Johnsson, Hui Yao, June Zhao, Changyu Pan
OBJECTIVE: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c 8.0-12.0%). RESEARCH DESIGN AND METHODS: In this multicenter, double-blind, active-controlled study (The START study: NCT02273050), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo, or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/day over 8 weeks...
September 19, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28921862/efficacy-and-safety-of-the-addition-of-ertugliflozin-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-with-metformin-and-sitagliptin-the-vertis-sita2-placebo-controlled-randomized-study
#13
Samuel Dagogo-Jack, Jie Liu, Roy Eldor, Guillermo Amorin, Jeremy Johnson, Darcy Hille, Yuqin Liao, Susan Huyck, Gregory Golm, Steven G Terra, James P Mancuso, Samuel S Engel, Brett Lauring
AIMS: To assess ertugliflozin in patients with type 2 diabetes inadequately controlled on metformin and sitagliptin. MATERIALS AND METHODS: In this double-blind randomized study (NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0-10.5% [53-91 mmol/mol] on metformin ≥1500 mg/day and sitagliptin 100 mg/day; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2) ) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily, or placebo. Primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52...
September 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28905478/efficacy-and-safety-of-alirocumab-in-insulin-treated-individuals-with-type-1-or-type-2-diabetes-and-high-cardiovascular-risk-the-odyssey-dm-insulin-randomized-trial
#14
Lawrence A Leiter, Bertrand Cariou, Dirk Müller-Wieland, Helen M Colhoun, Stefano Del Prato, Francisco J Tinahones, Kausik K Ray, Maja Bujas-Bobanovic, Catherine Domenger, Jonas Mandel, Rita Samuel, Robert R Henry
AIMS: To investigate the efficacy and safety of alirocumab in participants with type 2 (T2D) or type 1 diabetes (T1D) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy. METHODS: Participants at high cardiovascular risk with T2D (n = 441) or T1D (n = 76) and LDL cholesterol levels ≥1.8 mmol/L (≥70 mg/dL) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks, for 24 weeks' double-blind treatment...
September 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28898514/risk-of-lower-extremity-amputations-in-people-with-type-2-diabetes-mellitus-treated-with-sodium-glucose-co-transporter-2-inhibitors-in-the-usa-a-retrospective-cohort-study
#15
Zhong Yuan, Frank J DeFalco, Patrick B Ryan, Martijn J Schuemie, Paul E Stang, Jesse A Berlin, Mehul Desai, Norm Rosenthal
AIMS: To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non-SGLT2 inhibitor antihyperglycaemic agents (AHAs). MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2 inhibitors or non-SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non-SGLT2 inhibitor AHAs...
September 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28895655/insulin-resistance-and-cardiovascular-outcomes-in-the-origin-trial
#16
Hertzel C Gerstein, Ele Ferrannini, Matthew C Riddle, Salim Yusuf
AIMS: In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, titrated doses of basal insulin glargine targeting fasting normoglycemia had a neutral effect on cardiovascular outcomes. The dose of insulin required to achieve normoglycemia provides a unique measurement of each individual's resistance to insulin's action, and was therefore used to examine the link between insulin resistance and cardiovascular outcomes. MATERIALS AND METHODS: Self-titration of insulin doses targeting a fasting plasma glucose < 5...
September 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28892258/sitagliptin-and-roux-en-y-gastric-bypass-modulate-insulin-secretion-via-regulation-of-intra-islet-pyy
#17
Claudia Guida, Laura J McCulloch, Mahdieh Godazgar, Sam D Stephen, Charlotte Baker, Davide Basco, Jiawen Dong, Duan Chen, Anne Clark, Reshma D Ramracheya
AIMS: The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme DPP-IV has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS)...
September 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28884949/estimated-glucose-disposal-rate-predicts-mortality-in-adults-with-type-1-diabetes
#18
Thomas Nyström, Martin J Holzmann, Björn Eliasson, Ann-Marie Svensson, Ulrik Sartipy
AIMS: This study aimed to investigate the association between insulin resistance as determined by the estimated glucose disposal rate (eGDR), and survival in adults with type 1 diabetes (T1D) in Sweden. MATERIAL AND METHODS: Using the Swedish National Diabetes Register, people with T1D were included from January 1, 2005 to December 31, 2012. Outcomes were retrieved from National healthcare registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the associations between eGDR (mg/kg/min) categorized into <4, 4-5...
September 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28862812/performance-of-individually-measured-vs-population-based-c-peptide-kinetics-to-assess-%C3%AE-cell-function-in-presence-and-absence-of-acute-insulin-resistance
#19
Ron T Varghese, Chiara Dalla Man, Marcello C Laurenti, Francesca Piccinini, Anu Sharma, Meera Shah, Kent R Bailey, Robert A Rizza, Claudio Cobelli, Adrian Vella
AIMS: Standardized, population-based kinetics of C-peptide distribution and clearance are used to estimate insulin secretion from plasma C-peptide concentrations without direct measurement of C-peptide kinetics. We then compared the performance of population-based kinetics to directly measured C-peptide kinetics when used to calculate β-cell responsivity indices. To ensure that population-based kinetics apply to all conditions where β-cell function is measured, subjects were studied in the presence and absence of acute insulin resistance...
September 1, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28862808/comparative-effectiveness-of-once-weekly-glp-1-receptor-agonists-on-6-month-glycemic-control-and-weight-outcomes-in-patients-with-type-2-diabetes
#20
Sudhir Unni, Eric Wittbrodt, Junjie Ma, Marisa Schauerhamer, Jeff Hurd, Natalia Ruiz-Negrón, Carrie McAdam-Marx
A retrospective cohort study was conducted in patients with type 2 diabetes (T2D) in an electronic medical record database to compare real-world, 6-month A1C and weight outcomes for exenatide QW (EQW) vs. dulaglutide and vs. albiglutide. The study included 2,133 EQW, 201 dulaglutide, and 131 albiglutide patients. Overall mean (SD) age was 60 (11) years and 54% were men; neither differed between comparison groups. Mean baseline A1C was similar for EQW [8.3 (1.7)%] and dulaglutide [8.5 (1.5)% (p=0.165)], but higher for albiglutide [8...
September 1, 2017: Diabetes, Obesity & Metabolism
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