Author: "Poulter, Neil R." / Topic: hypoglycemic agents - Searchworks@Jio Institute Digital Library Search Results

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1. Safety of Liraglutide in Type 2 Diabetes and Chronic Kidney Disease.

Author: Mann JFE, Fonseca VA, Poulter NR, Raz I, Idorn T, Rasmussen S, von Scholten BJ, and Mosenzon O
Subjects: Aged, Biomarkers blood, Blood Glucose metabolism, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnosis, Double-Blind Method, Female, Glucagon-Like Peptide-1 Receptor agonists, Glucagon-Like Peptide-1 Receptor metabolism, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents adverse effects, Incretins adverse effects, Liraglutide adverse effects, Male, Middle Aged, Renal Insufficiency, Chronic diagnosis, Time Factors, Treatment Outcome, Blood Glucose drug effects, Diabetes Mellitus, Type 2 drug therapy, Glomerular Filtration Rate, Hypoglycemic Agents therapeutic use, Incretins therapeutic use, Kidney physiopathology, Liraglutide therapeutic use, Renal Insufficiency, Chronic physiopathology
Abstract: Background and Objectives: The glucagon-like peptide-1 receptor agonist liraglutide demonstrated cardiovascular and kidney benefits in the LEADER trial, particularly in participants with CKD., Design, Setting, Participants, & Measurements: This post hoc analysis evaluated the safety of liraglutide treatment in patients with CKD in LEADER. Overall, 9340 patients were randomized to liraglutide or placebo, both in addition to standard of care. Of those, 2158 patients had CKD versus 7182 without CKD (defined as eGFR <60 versus ≥60 ml/min per 1.73 m 2 , respectively); 966 patients had macroalbuminuria and 2456 had microalbuminuria (urine albumin-creatinine ratio >300 mg/g and ≥30 to ≤300 mg/g, respectively). At baseline, the mean eGFR in patients with CKD was 46±11 ml/min per 1.73 m 2 versus 91±22 ml/min per 1.73 m 2 in those without CKD. Time to first event within event groups was analyzed using Cox regression with treatment group, baseline eGFR group, or baseline albuminuria group as fixed factors., Results: Overall, serious adverse events were more frequently recorded in patients with CKD compared with those without CKD (59% versus 50%; interaction P =0.11); however, they occurred to the same extent in those on liraglutide versus placebo. Similarly, no interaction of adverse events with randomized therapy was observed in patients with micro- or macro- versus normoalbuminuria (interaction P =0.11). Risk of severe hypoglycemia was significantly reduced with liraglutide versus placebo in patients with CKD or with micro- or macroalbuminuria (hazard ratio, 0.63 [95% CI, 0.43 to 0.91] and 0.57 [95% CI, 0.40 to 0.82], respectively)., Conclusions: In LEADER, the use of liraglutide in those with CKD was safe, with no difference between patients with and without CKD., Clinical Trial Registry Name and Registration Number: ClinicalTrials.gov; NCT01179048 (https://clinicaltrials.gov/ct2/show/NCT01179048)., (Copyright © 2020 by the American Society of Nephrology.)
Published: 2020
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2. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure.

Author: Marso SP, Baeres FMM, Bain SC, Goldman B, Husain M, Nauck MA, Poulter NR, Pratley RE, Thomsen AB, and Buse JB
Subjects: Aged, Cardiovascular Diseases drug therapy, Cardiovascular Diseases mortality, Death, Double-Blind Method, Female, Hospitalization trends, Humans, Internationality, Male, Middle Aged, Treatment Outcome, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 mortality, Heart Failure drug therapy, Heart Failure mortality, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use
Abstract: Background: More data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required., Objectives: The purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history., Methods: In the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted., Results: At baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19)., Conclusions: Based on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048)., (Copyright © 2020. Published by Elsevier Inc.)
Published: 2020
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3. Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy: Evidence from the LEADER trial.

Author: Tack CJ, Jacob S, Desouza C, Bain SC, Buse JB, Nauck MA, Petrie JR, Poulter NR, Pratley RE, Stegmann HVBK, Bosch-Traberg H, Startseva E, and Zinman B
Subjects: Aged, Female, Glycated Hemoglobin analysis, Humans, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents therapeutic use, Insulin administration & dosage, Insulin therapeutic use, Liraglutide administration & dosage, Liraglutide therapeutic use, Male, Middle Aged, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptide-1 Receptor agonists, Hypoglycemic Agents adverse effects, Insulin adverse effects, Liraglutide adverse effects
Abstract: Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial., Materials and Methods: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy., Results: At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal-only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P < .001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups., Conclusions: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
Published: 2019
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4. Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus.

Author: Berkelmans GFN, Gudbjörnsdottir S, Visseren FLJ, Wild SH, Franzen S, Chalmers J, Davis BR, Poulter NR, Spijkerman AM, Woodward M, Pressel SL, Gupta AK, van der Schouw YT, Svensson AM, van der Graaf Y, Read SH, Eliasson B, and Dorresteijn JAN
Subjects: Aged, Cohort Studies, Disease-Free Survival, Female, Humans, Male, Middle Aged, Myocardial Infarction etiology, Myocardial Infarction prevention & control, Prognosis, Stroke etiology, Stroke prevention & control, Time Factors, Antihypertensive Agents therapeutic use, Aspirin therapeutic use, Cardiovascular Diseases etiology, Cardiovascular Diseases prevention & control, Diabetes Complications prevention & control, Diabetes Mellitus, Type 2 complications, Hypoglycemic Agents therapeutic use, Hypolipidemic Agents therapeutic use
Abstract: Aims: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke., Methods and Results: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment., Conclusion: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
Published: 2019
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5. Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10).

Author: Brown-Frandsen K, Emerson SS, McGuire DK, Pieber TR, Poulter NR, Pratley RE, Zinman B, Ranthe MF, Grøn R, Lange M, Moses AC, Örsy P, and Buse JB
Subjects: Humans, Middle Aged, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents adverse effects, Hypoglycemic Agents therapeutic use, Insulin, Long-Acting administration & dosage, Insulin, Long-Acting adverse effects, Insulin, Long-Acting therapeutic use, Liraglutide administration & dosage, Liraglutide adverse effects, Liraglutide therapeutic use
Abstract: Aim: To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE)., Materials and Methods: Patients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses were adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease., Results: At baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [0.62 (0.41; 0.92) 95%CI ] and all-cause mortality [0.50 (0.29; 0.88) 95%CI ]. There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results., Conclusions: Use of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
Published: 2019
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6. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke.

Author: Verma S, Poulter NR, Bhatt DL, Bain SC, Buse JB, Leiter LA, Nauck MA, Pratley RE, Zinman B, Ørsted DD, Monk Fries T, Rasmussen S, and Marso SP
Subjects: Aged, Canada epidemiology, Diabetes Mellitus, Type 2 epidemiology, Female, Follow-Up Studies, Humans, Incidence, Male, Maximum Tolerated Dose, Middle Aged, Myocardial Infarction epidemiology, Proportional Hazards Models, Risk, Stroke epidemiology, Survival Analysis, Treatment Outcome, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use, Myocardial Infarction drug therapy, Stroke drug therapy
Abstract: Background: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke., Methods: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone., Results: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, P interaction =0.11). Similar results were seen for secondary outcomes across risk groups., Conclusions: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.
Published: 2018
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7. Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease: Results of the LEADER Trial.

Author: Verma S, Bhatt DL, Bain SC, Buse JB, Mann JFE, Marso SP, Nauck MA, Poulter NR, Pratley RE, Zinman B, Michelsen MM, Monk Fries T, Rasmussen S, and Leiter LA
Subjects: Aged, Cardiovascular Diseases diagnosis, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 complications, Female, Humans, Male, Middle Aged, Placebo Effect, Proportional Hazards Models, Risk Factors, Survival Rate, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use, Vascular Diseases complications
Published: 2018
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8. Type 2 Diabetes and the Reduction of Cardiovascular Risk: Sorting Out the Actors and the Roles.

Author: Feldman RD, Fitchett D, Hegele RA, and Poulter NR
Subjects: Age of Onset, Blood Glucose Self-Monitoring methods, Causality, Disease Progression, Humans, Prognosis, Risk Assessment, Risk Reduction Behavior, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 therapy, Hypoglycemic Agents pharmacology
Published: 2018
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9. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis.

Author: Bethel MA, Patel RA, Merrill P, Lokhnygina Y, Buse JB, Mentz RJ, Pagidipati NJ, Chan JC, Gustavson SM, Iqbal N, Maggioni AP, Öhman P, Poulter NR, Ramachandran A, Zinman B, Hernandez AF, and Holman RR
Subjects: Cardiovascular Diseases prevention & control, Humans, Prognosis, Survival Rate, Cardiovascular Diseases mortality, Cardiovascular System drug effects, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptide-1 Receptor agonists, Hypoglycemic Agents therapeutic use
Abstract: Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide., Methods: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes., Findings: Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0·90, 95% CI 0·82-0·99; p=0·033), a 13% RRR in cardiovascular mortality (0·87, 0·79-0·96; p=0·007), and a 12% relative risk reduction in all-cause mortality (0·88, 0·81-0·95; p=0·002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo., Interpretation: Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs., Funding: Amylin Pharmaceuticals (AstraZeneca)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Published: 2018
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10. Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2).

Author: Zinman B, Marso SP, Poulter NR, Emerson SS, Pieber TR, Pratley RE, Lange M, Brown-Frandsen K, Moses A, Ocampo Francisco AM, Barner Lekdorf J, Kvist K, and Buse JB
Subjects: Aged, Blood Glucose drug effects, Double-Blind Method, Fasting blood, Female, Humans, Insulin therapeutic use, Male, Middle Aged, Prospective Studies, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemia blood, Hypoglycemia drug therapy, Hypoglycemic Agents therapeutic use
Abstract: Aims/hypothesis: The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) was a double-blind, randomised, event-driven, treat-to-target prospective trial comparing the cardiovascular safety of insulin degludec with that of insulin glargine U100 (100 units/ml) in patients with type 2 diabetes at high risk of cardiovascular events. This paper reports a secondary analysis investigating associations of day-to-day fasting glycaemic variability (pre-breakfast self-measured blood glucose [SMBG]) with severe hypoglycaemia and cardiovascular outcomes., Methods: In DEVOTE, patients with type 2 diabetes were randomised to receive insulin degludec or insulin glargine U100 once daily. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In this article, day-to-day fasting glycaemic variability was based on the standard deviation of the pre-breakfast SMBG measurements. The variability measure was calculated as follows. Each month, only the three pre-breakfast SMBG measurements recorded before contact with the site were used to determine a day-to-day fasting glycaemic variability measure for each patient. For each patient, the variance of the three log-transformed pre-breakfast SMBG measurements each month was determined. The standard deviation was determined as the square root of the mean of these monthly variances and was defined as day-to-day fasting glycaemic variability. The associations between day-to-day fasting glycaemic variability and severe hypoglycaemia, MACE and all-cause mortality were analysed for the pooled trial population with Cox proportional hazards models. Several sensitivity analyses were conducted, including adjustments for baseline characteristics and most recent HbA 1c ., Results: Day-to-day fasting glycaemic variability was significantly associated with severe hypoglycaemia (HR 4.11, 95% CI 3.15, 5.35), MACE (HR 1.36, 95% CI 1.12, 1.65) and all-cause mortality (HR 1.58, 95% CI 1.23, 2.03) before adjustments. The increased risks of severe hypoglycaemia, MACE and all-cause mortality translate into 2.7-, 1.2- and 1.4-fold risk, respectively, when a patient's day-to-day fasting glycaemic variability measure is doubled. The significant relationships of day-to-day fasting glycaemic variability with severe hypoglycaemia and all-cause mortality were maintained after adjustments. However, the significant association with MACE was not maintained following adjustment for baseline characteristics with either baseline HbA 1c (HR 1.19, 95% CI 0.96, 1.47) or the most recent HbA 1c measurement throughout the trial (HR 1.21, 95% CI 0.98, 1.49)., Conclusions/interpretation: Higher day-to-day fasting glycaemic variability is associated with increased risks of severe hypoglycaemia and all-cause mortality., Trial Registration: ClinicalTrials.gov NCT01959529.
Published: 2018
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11. Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal.

Author: Vora J, Ray K, Kosiborod M, Poulter NR, Rajagopalan S, and Leiter LA
Subjects: Clinical Trials as Topic statistics & numerical data, Diabetes Mellitus, Type 2 epidemiology, Humans, Hypoglycemic Agents classification, Incretins therapeutic use, Insulin analogs & derivatives, Insulin therapeutic use, Metformin therapeutic use, Neoplasms epidemiology, Risk Factors, Thiazolidinediones therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Neoplasms chemically induced
Abstract: Aim: A clinical appraisal of existing scientific literature sought to assess the need for long-term prospective epidemiological studies to investigate an increased cancer risk of anti-hyperglycemic medication in type 2 diabetes., Method: A focus statement was formulated as: "With a higher risk of cancers in patients with type 2 diabetes, all anti-hyperglycemic drugs should undergo long-term, prospective epidemiological studies for cancer risks." Field surveys were sent to practicing physicians and endocrinologists to identify the currently prevalent level of acceptance of this statement. Subsequently, a meeting with a six-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This publication reviews the publications and discussion points brought forth in this meeting and their effect on statement acceptance by the panel., Results: Whereas the majority of field survey responders primarily agreed with the statement, panel members were divided in their statement support. This division remained intact after review of the literature., Conclusions: While there was evidence that type 2 diabetes is associated with an increased risk of cancer, existing studies seemed insufficient to definitively demonstrate a link between cancer risk and use of specific anti-hyperglycemic therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)
Published: 2017
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12. Liraglutide and Renal Outcomes in Type 2 Diabetes.

Author: Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, and Buse JB
Subjects: Acute Kidney Injury prevention & control, Aged, Albuminuria prevention & control, Creatinine blood, Diabetic Nephropathies mortality, Diabetic Nephropathies prevention & control, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Hypoglycemic Agents adverse effects, Intention to Treat Analysis, Kidney Failure, Chronic prevention & control, Liraglutide adverse effects, Male, Middle Aged, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies drug therapy, Glucagon-Like Peptide 1 agonists, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use
Abstract: Background: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown., Methods: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed., Results: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively)., Conclusions: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
Published: 2017
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13. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.

Author: Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, Pratley RE, Haahr PM, Lange M, Brown-Frandsen K, Moses A, Skibsted S, Kvist K, and Buse JB
Subjects: Aged, Blood Glucose analysis, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Double-Blind Method, Female, Humans, Hypoglycemia chemically induced, Hypoglycemic Agents therapeutic use, Incidence, Insulin Glargine therapeutic use, Insulin, Long-Acting therapeutic use, Kaplan-Meier Estimate, Male, Middle Aged, Cardiovascular Diseases chemically induced, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents adverse effects, Insulin Glargine adverse effects, Insulin, Long-Acting adverse effects
Abstract: Background: Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec., Methods: We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome., Results: Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups., Conclusions: Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).
Published: 2017
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14. Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) - DEVOTE 1.

Author: Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, Pratley RE, Haahr PM, Lange M, Frandsen KB, Rabøl R, and Buse JB
Subjects: Aged, Angina, Unstable epidemiology, Comorbidity, Coronary Disease epidemiology, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 metabolism, Double-Blind Method, Female, Glycated Hemoglobin metabolism, Heart Failure epidemiology, Hospitalization statistics & numerical data, Humans, Hypoglycemia chemically induced, Male, Middle Aged, Myocardial Infarction epidemiology, Proportional Hazards Models, Renal Insufficiency, Chronic epidemiology, Risk Factors, Stroke epidemiology, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Insulin Glargine therapeutic use, Insulin, Long-Acting therapeutic use
Abstract: DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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15. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.

Author: Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, and Buse JB
Subjects: Aged, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 mortality, Double-Blind Method, Female, Gastrointestinal Diseases chemically induced, Humans, Hypoglycemic Agents adverse effects, Liraglutide adverse effects, Male, Middle Aged, Myocardial Infarction epidemiology, Stroke epidemiology, Treatment Outcome, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use
Abstract: Background: The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown., Methods: In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes., Results: A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group., Conclusions: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.).
Published: 2016
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16. LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial.

Author: Petrie JR, Marso SP, Bain SC, Franek E, Jacob S, Masmiquel L, Leiter LA, Haluzik M, Satman I, Omar M, Shestakova M, Van Gaal L, Mann JF, Baeres FM, Zinman B, and Poulter NR
Subjects: Aged, Antihypertensive Agents therapeutic use, Blood Pressure, Diabetes Mellitus, Type 2 complications, Double-Blind Method, Female, Glucagon-Like Peptide-1 Receptor antagonists & inhibitors, Humans, Hypertension complications, Liraglutide adverse effects, Male, Middle Aged, North America, Risk Factors, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 physiopathology, Hypertension drug therapy, Hypertension physiopathology, Hypoglycemic Agents therapeutic use, Liraglutide therapeutic use
Abstract: Objective: As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial., Methods: We analyzed baseline data from LEADER (NCT01179048), an ongoing phase 3B, randomized, double-blind, placebo-controlled cardiovascular outcomes trial examining the cardiovascular safety of the glucagon-like peptide-1 receptor agonist liraglutide in 9340 people with T2DM from 32 countries [age (all mean ± SD) 64 ± 7.2 years, BMI 32.5 ± 6.3 kg/m, duration of diabetes 12.7 ± 8.0 years], all of whom were at high risk for cardiovascular disease (CVD)., Results: A total of 81% (n = 7592) of participants had prior CVD and 90% (n = 8408) had a prior history of hypertension. Despite prescription of multiple antihypertensive agents at baseline, only 51% were treated to a target BP of less than 140/85 mmHg and only 26% to the recommended baseline BP target of less than 130/80 mmHg. In univariate analyses, those with prior CVD were prescribed more agents (P < 0.001) and had lower BP than those without (137 ± 18.8/78 ± 10.6 mmHg versus 140 ± 17.7/80 ± 9.9 mmHg; P < 0.001). In logistic regression analyses, residency in North America (64% treated to <140/85 mmHg; 38% treated to <130/80 mmHg) was the strongest predictor of BP control., Conclusion: These contemporary data confirm that BP remains insufficiently controlled in a large proportion of individuals with T2DM at high cardiovascular risk, particularly outside North America. Longitudinal data from the LEADER trial may provide further insights into BP control in relation to cardiovascular outcomes in this condition.
Published: 2016
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17. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

Author: Marso SP, Poulter NR, Nissen SE, Nauck MA, Zinman B, Daniels GH, Pocock S, Steinberg WM, Bergenstal RM, Mann JF, Ravn LS, Frandsen KB, Moses AC, and Buse JB
Subjects: Aged, Cardiovascular Diseases drug therapy, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 mortality, Double-Blind Method, Female, Glucagon-Like Peptide 1 adverse effects, Glucagon-Like Peptide 1 therapeutic use, Humans, Hypoglycemic Agents adverse effects, Liraglutide, Male, Middle Aged, Research Design, Treatment Outcome, Cardiovascular Diseases complications, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptide 1 analogs & derivatives, Hypoglycemic Agents therapeutic use
Abstract: Background: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM)., Study Design: To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke., Conclusions: LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM., (© 2013.)
Published: 2013
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18. Blood pressure and glucose control in subjects with diabetes: new analyses from ADVANCE.

Author: Poulter NR
Subjects: Aged, Antihypertensive Agents therapeutic use, Diabetes Mellitus, Type 2 therapy, Drug Combinations, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Blood Glucose analysis, Blood Pressure, Diabetes Complications prevention & control, Diabetes Mellitus, Type 2 physiopathology, Gliclazide therapeutic use, Hypoglycemic Agents therapeutic use, Indapamide therapeutic use, Perindopril therapeutic use
Abstract: Objectives: To evaluate among individuals with diabetes whether major microvascular and macrovascular events are reduced by: (1) blood pressure lowering with a perindopril/indapamide combination compared with placebo; (2) intensive glucose control (targeting a haemoglobin A1c level of < or =6.5%) with a gliclazide MR-based regimen, compared with usual care., Methods: Participants with diabetes aged 55 years and older with at least one additional vascular risk factor were randomly assigned, using a 2 x 2 factorial design, to additional blood pressure lowering versus placebo and intensive versus standard glucose control. The primary outcomes were macrovascular (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) and microvascular (new or worsening nephropathy or retinopathy) events jointly and separately., Results: A total of 11 140 participants were randomly assigned to the blood pressure and glucose-lowering arms, which ended after 4.3 and 5.5 years, respectively. The effects of the two interventions were independent and additive on prespecified endpoints. Compared with placebo, additional blood pressure lowering of 5.6/2.2 mmHg was associated with reductions of 9% in the primary endpoint (P = 0.041), 18% in cardiovascular death (P = 0.027), 14% in total mortality (P = 0.025), and 21% in total renal events (P < 0.01). Compared with standard glucose control, intensive control (mean in-trial 0.67 percentage point reduction in haemoglobin A1c level) was associated with reductions of 10% in the primary endpoint (P = 0.013), 14% in major microvascular events (P = 0.01) and 11% in total renal events (P < 0.001)., Conclusion: Additional blood pressure lowering and intensive glucose control, as achieved in ADVANCE, produce independent benefits and, when combined, substantially reduced cardiovascular mortality and all-cause mortality and improved renal outcomes.
Published: 2009
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19. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

Author: Marso, Steven P., McGuire, Darren K., Zinman, Bernard, Poulter, Neil R., Emerson, Scott S., Pieber, Thomas R., Pratley, Richard E., Haahr, Poul-Martin, Lange, Martin, Brown-Frandsen, Kirstine, Moses, Alan, Skibsted, Simon, Kvist, Kajsa, Buse, John B., Hansen, Liliana, Rabol, Rasmus, Bethel, Angelyn, de Lemos, James A., Senn, Stephen, Schwamm, Lee, Timmis, Adam, Alshekhlee, Amer, Bach, Richard G., Bertram, Therese M., Chaitman, Bernard R., Cruz-Flores, Salvador, Eckstein, Jane F., Feen, Eliahu S., Fisher, Simon J., Gosselin, Gilbert, Lim, Michael J., Rosenzweig, James L., Sherwin, Robert S., Tobin, Garry S., Vetrovec, George, Ziemer, David C., Daugaard, Gedske, Ozlem, Er, Pollak, Michael, Sengelov, Lisa, Ahn, Yu-Bae, Amod, Aslam, Benroubi, Mariana, Boonyavarakul, Apussanee, Canecki-Varzic, Silvija, Consoli, Agostino, Eliaschewitz, Freddy G., Franek, Edward, Jinnouchi, Hideaki, Khokhlov, Alexander L., Mithal, Ambrish, Philis-Tsimikas, Athena, Ong, Tiong Kiam, Pop, Lavinia, Reyna, Leobardo Sauque, Rodbard, Helena W., Roula, Daoud, Saravanan, Ponnusamy, Sesti, Giorgio, Sorli, Christopher, Sposetti, Georgina, Tinahones-Madueno, Francisco-Jose, Woo, Vincent, Berard, Lori, Caballero Mateos, Irene, Cooper, Alison, DeLuca, Clarisa, Fillary, Julie, Gan, Diyana Gan Abdul Rahman, Goondiwala, Amina, Tapia, Jessica, Busch, Robert, Chaykin, Louis, Hollander, Priscilla, Karounos, Dennis, Lane, Wendy, Lingvay, Ildiko, Odugbesan, A. Ola, Ohlson-Elliott, Theresa, Ovalle, Fernando, Pantalone, Kevin M., Phelps, Spencer, Pop-Busui, Rodica, Robertson, David, Shlesinger, Yshay, Silver, Robert, Warren, Mark, Arrar, Mohammed, Belkheir, Hassani, Benabbas, Youcef, Benferhat, Schahrazed, Benoun, Fatima, Bensalem, Samia, Bourezane, Samia, Elaoufi, Selmane Rafik, Gourine, Mouna, Hadjhabib, Mohamed, Hadjhamou, Fouzia, Hakem, Jamila, Kaouache, Nadjib, Khensal, Sabrina, Kitouni, Yacine, Lakhal, Lamine, Lezzar, Al-Kassem, Meftah, Imane Aicha, Mehenni, Lahouaria, Nouri, Nassim, Oumerzouk, Fatma, Sakouhi, Mounia, Talha, Kheira, Zemri, Zouaouia, Caeiro, Gabriela, Calveyra, Martha, Cluigt, Natalia, Geronazzo, Veronica, Lema, Silvina, Monferran, Pablo Martinez, Oviedo, Alejandra, Pozzi, Jose, Sala, Jorgelina, Schindler, Ana, Sernia, Virginia, Sicer, Maximiliano, Solis, Silvana, Varela, Patricia, Waitman, Jorge, Augusto, Gustavo Akerman, Alves, Breno, Alves, Erica, Barbosa, Luciana, Bona, Renata, Borges, Joao, Bosco, Adriana, Canani, Luis, Castro, Denise, Cavalcante, Lilian, Cechin, Laura, Cercato, Cintia, Chrisman, Carlos, Chrisman, Carolina, Cintra, Rebecca, Costa, Giselle, Fontenele, Ana Paula, Forti, Adriana, Francisco, Beatriz, Franco, Denise, Genestreti, Paulo, Gross, Jorge, Haddad, Ludmila, Halpern, Alfredo, Hissa, Miguel, Leanca, Camila, Leao, Beatriz, Marinho, Ana Elisabeth, Miranda, Isabela, Nunes, Adriano, Palhares, Fabiana, Poco, Christiani, Salles, Joao, Sampaio, Celia, Santomauro Jr., Augusto, Sartori, Carla, Sena, Rita, da Silva, Marina, da Silva, Paula, Siqueira, Katia, Turatti, Luiz, Valenti, Adriana, Vasques, Enio, Vencio, Sergio, Visconti, Guilherme, Belanger, Andre, Chilvers, Martyn, Dumas, Richard, Hurd, Carmen, Lafleche, Francois, Lam, Paul, Martinho, Valdemar, Palardy, Jean, Peterson, Sean, Raff, Errol, Sinnaeve, Linda, Sullivan, David, Baraban, Vedrana, Blaslov, Kristina, Bulum, Tomislav, Varzic, Silvija Canecki, Berkovic, Maja Cigrovski, Balen, Marica Jandric, Kruljac, Ivan, Lesnjakovic, Silvija, Lucijanic, Tomo, Majic, Ana, Rahelic, Dario, Smircic-Duvnjak, Lea, Vrkljan, Milan, Zibar, Karin, Zukanovic, Sidbela, Athanasopoulou, Elpida, Benis, Apostolos, Benroubi, Marian, Diakoumopoulou, Evanthia, Doupis, John, Griva, Theodora, Kazakos, Kyriakos, Kypraios, Nikolaos, Liatis, Stavros, Makrilakis, Konstantinos, Markou, Athina, Pagkalos, Emmanouil, Papanastasiou, Labrini, Piaditis, George, Sampanis, Christos, Siami, Evangelia, Tentolouris, Nikolaos, Tsiama, Vasiliki, Zografou, Ioanna, Adling, Pravishal, Ali, Mazher, Anjana, R. M., Arora, Arpita, Ayyar, Vageesh, Banerjee, Suvro, Bantwal, Ganapathi, Bhagwat, Nikhil, Bhattacharyya, Arpandev, Bhawarlal, Anandakumar, Chakraborty, Rabin, Chatterjee, Sanjay, Chaudhury, Tirthankar, Chowdhury, Subhankar, Damelia, Priyal, Das, Mrinal, Das, Sambit, Desai, Ankush, Devru, Nandani, Farooqui, Khalid, Ganie, Mohd Ashraf, George, Belinda, Ghosh, Debasis, Girithara, Gopalakrishnan, Haribhai, Zinzuwadia, Jain, Nupur, Jassar, Amandeep, Joshi, Ameya, Kale, Dilip, Kale, Shailaja, Kelwade, Jayant, Khatri, Ashok, Kulshreshtha, Bindu, Majumder, Bikas, Manikath, Neeraj, Margekar, Shubhalaxmi, Marwah, Tiven, Mathew, Vivek, Moulick, N. D., Mutha, Abhay, Muthu, Ramuu, Nalawade, Asmitha, Narvencar, Kedareshwar, Pandit, Kaushik, Pangtey, Ghanshyam, Parthasarathy, B., Phatak, Sanjeev, Prakash, Anupam, Prusty, Pitambar, Radhakrishnan, Chandni, Raja, Indu, Ravikumar, Ranjani, Saboo, Banshi, Sachdeva, Isha, Sangeetha, S., Selvam, Kasthuri, Sethi, Bipin, Shah, Asha, Shah, Harshal K., Shah, Priyanshu, Shah, Rushit, Shaikh, Sajid, Shaikh, Shehla, Singh, K. P., Sivagnanam, Nallaperumal, Tandon, Nikhil, Thonangi, Rajesh, Thulaseedharan, N., Toraskar, Kedar, Varthakavi, Premalatha, Yadav, Sameer, Andreozz, Francesco, Arturi, Franco, Baldassarre, Maria Pompea Antonia, Barone, Milena, Bonura, Alice, Bucciarelli, Loredana, Buscemi, Chiara, Buscemi, Silvio, Carnovale, Anna, Caselli, Chiara, Ceci, Gloria, Cimino, Elena, Colella, Alessandra, Crippa, Valentina, Cufone, Sabrina, D'Erasmo, Laura, De Remigis, Alessandra, Di Bartolo, Paolo, Dionisio, Rosa, Disoteo, Olga, Fabietti, Marcella, Febo, Fabrizio, Filetti, Sebastiano, Genovese, Stefano, Ginestra, Federica, Grancini, Valeria, Grieco, Elvira, Magistro, Andrea, Maranghi, Marianna, Monti, Lucilla, Orsi, Emanuela, Pellicano, Francesca, Pergolini, Daniela, Perticone, Francesca, Piatti, PierMarco, Pizzi, Gianluigi, Rondinelli, Maurizio, Rossi, Margherita, Rubino, Mariangela, Setola, Emanuela, Succurro, Elena, Tarquini, Giovanna, Tiseo, Giusy, Tonolo, Giancarlo, Villa, Valentina, Hong, Stefania Vo, Amano, Kazushi, Hachiya, Remi, Hieshima, Kunio, Hirao, Koichi, Hisatake, Tomoko, Honda, Ritsuko, Ihana, Noriko, Inoue, Kaori, Iwamoto, Yasuhiko, Jinnouchi, Tomio, Kajiwara, Keizou, Kawazu, Shoji, Kikuchi, Masatoshi, Kikuchi, Takako, Koike, Yoko, Komatsu, Mitsuhisa, Kumakura, Atsushi, Kurinami, Noboru, Kushiyama, Akifumi, Maeda, Hajime, Matsuda, Toshihisa, Nakamura, Shuji, Nakayama, Koujin, Nishio, Shin-ichi, Onishi, Yukiko, Sato, Nobuyuki, Sato, Yoshihiko, Shirabe, Shinichiro, Sugiyama, Seigo, Suzuki, Tomoko, Tahara, Tazu, Takao, Toshiko, Takei, Masahiro, Takemoto, Ikutaka, Takeshige, Keiko, Tanaka, Kentaro, Taniguchi, Shotaro, Tsujimoto, Tetsuro, Tsukuda, Katsunori, Wakabayashi, Sayaka, Yamazaki, Masanori, Yoshida, Yoko, Yoshimoto, Ayako, Abidin, Imran Zainal, Abdullah, Shahrin Tarmizi Che, Adam, Noor Lita, Ahmad, Madihah, Ahmad, Nik Nur Fatnoon Nik, Amin, Nor Hanim Mohd, Aw, Cheng Yew, Cham, Yee Ling, Chong, Hui Min, Chua, Seng Keong, Fauzi, Sharifah Aisyah Shahabudin Syed Ahmad, Fong, Alan Yean Yip, Ghapar, Abd Kahar Abd, Hanafi, Norliza, Abu Hassan, Muhammad Radzi, Iberahim, Rahimah, Khiew, Ning Zan, Lee, Gary Chin Keong, Lingam, Rakesh, Long, Richard Chay Shien, Mahendran, Kauthaman A., Oon, Yen Yee, Said, Asri, Sothiratnam, Radhakrishna, Sridhar, Ganiga Srinivasiah, Suan, Mohd Azri Mohd, Tan, Sian Kong, Tey, Julian Hock Chuan, Undok, Abdul Wahab, Waid, Anuar, Vijayasingham, Shalini, Voon, Chi Yen, Yew, Kuan Leong, Yong, Lit Sin, Aguilar-Parra, Lilia, Aguirre, Karen, Alvarez-Carrillo, Rebeca, Arechavaleta-Granell, Maria, Baez-Campos, Aurelia, Bayram Llamas, Edmundo Alfredo, Calvo-Vargas, Cesar, Cedano-Limon, Marielena, Beltran Jaramillo, Teresita de Jesus, de Jesus Marin-Lopez, Jose, Ruiz Cornejo, Maria de Jesus, Juarez Cervantes, Maria del Carmen, Estevez de Alba, Isabel, Estrada Garcia, Raul, Estrada, Suellen, Garza-Vergara, Marisol, Gonzalez-Perez, Rosa, Gonzalez-Valencia, Carlos, Guerrero-Reyes, Rosalinda, Haro Ortiz, Jose Alfredo, Hernandez Salazar, Eduardo, Illescas Diaz, Iris, Illescas Diaz, Jesus, Loredo, Imelda, Jimenez-Ramos, Silvia, Larios-Mora, Diana, Lopez Garcia, Maria Elena, Lopez-Serrano, Julieta, Martinez-Nolasco, Bertha, Nunez Marquez, Ricardo, Pacheco Aranda, Elizabeth, Peralta-Cantu, Irving, Perez Chagollan, Ana, Ramirez, Maria, Robledo Duron, Israel, Rodriguez Briones, Ignacio, Rodriguez, Maria, Sauque Reyna, Leobardo, Vazquez-Ceja, Adriana, Vera-Bocanegra, Alejandro, Vidrio Velazquez, Maricela, Contreras Sandoval, Aleida Yael, Bartelik, Karol, Bilska, Aleksandra, Biniszkiewicz, Tomasz, Bogdanski, Pawel, Chamienia, Agnieszka, Cieslak-Puchalska, Anna, Czochra, Wojciech, Gajewski, Bogdan, Gromniak, Elwira, Holda, Ewa, Jaskulska-Gorzelewska, Barbara, Jedynasty, Krystyna, Kloda, Elzbieta, Kmak-Balawender, Beata, Kobielusz-Gembala, Iwona, Konieczny, Marek, Kramarczuk, Elzbieta, Kuleta, Jerzy, Lesniewski, Robert, Lominska, Teresa, Lukaszewicz, Monika, Majewska, Izabella, Mlynarski, Tomasz, Mostowy, Aleksandra, Rybak, Anna, Skrypnik, Damian, Wolny, Malgorzata, Zmuda, Witold, Buduru, Alina Nicoleta, Cif, Adriana, Cozma, Mihaela, Crisan, Carmen, Barbonta, Cristian Gelu, Barbonta, Diana, Mihalcea, Madalina, Mociran, Mihaela, Muresan, Sorina, Popescu, Alexandrina, Pruna, Luchiana, Sandu, Nadia Ramona, Suleac, Oana Andreea, Vincze, Eva Cornelia, Andreeva, Elena, Berns, Svetlana, Barykina, Irina, Bernitcyna, Angela, Bezdenezhnykh, Natalia, Chumachek, Elena, Demarina, Svetlana, Didenko, Anna, Dubinina, Nadezhda, Dzherieva, Irina, Elsukova, Olga, Esenyan, Lev, Filippova, Ekaterina, Gabova, Nadezhda, Garina, Irina, Glikman, Yulia, Glova, Svetlana, Goncharova, Ekaterina, Gorbatova, Elena, Gordeev, Ivan, Grigorian, Inessa, Gromova, Svetlana, Ipatko, Irina, Karaban, Elena, Katushkina, Yulia, Kaygorodtseva, Olga, Kerova, Irina, Khaisheva, Larisa, Khmelnitskiy, Oleg, Khokhlov, Alexander, Khokhlov, Mikhail, Khorolets, Ekaterina, Klyuenkova, Elena, Konovalova, Olga, Korneva, Ksenia, Kosmacheva, Elena, Kunitsyna, Marina, Kupriyanova, Tatiana, Kuznetsova, Natalia, Lantseva, Olga, Ledyaeva, Alla, Lileeva, Elena, Markovich, Alexander, Martirosian, Narine, Maslova, Alisa, Milyukova, Galina, Mokhova, Irina, Nagirniak, Olga, Nastina, Elena, Nedogoda, Sergei, Orlova, Valeriia, Svetlana, Otarova, Ostapenko, Marina, Papaskiri, Nino, Pavlikova, Elena, Peskov, Andrey, Petrik, Galina, Petrov, Alexander, Petunina, Nina, Platonov, Dmitry, Poliakova, Yulia, Potapova, Zhanna, Pribylova, Svetlana, Razumovsky, Igor, Redkin, Alexander, Rodionova, Tatyana, Rudenko, Evgenia, Rykalina, Natalia, Salasyuk, Alla, Semikina, Tatiana, Serebryakova, Inna, Shanina, Larisa, Shmidt, Evgenia, Sinitsina, Olga, Smetanina, Svetlana, Smirnova, Marya, Smirnova, Victoria, Smolentseva, Nadezhda, Sobolev, Alexander, Soldatenkova, Anna, Soldatova, Yulia, Speshilova, Svetlana, Startseva, Olga, Strezhova, Larisa, Strongin, Leonid, Suplotova, Lyudmila, Suvorova, Daria, Tepaeva, Alisa, Trukhina, Liubov, Tyugaeva, Alisa, Vasyutkova, Olga, Vinokurova, Valentina, Yukhno, Elena, Yuzhakova, Natalia, Zagrebelnaya, Olga, Zalevskaya, Alsu, Zhukova, Elena, Aomar Millan, Ismael, Beltran Romero, Luis M., Ignacio Fernandez Navarro, Jose, Carlos Ferrer Garcia, Juan, Garcia Blasco, Lourdes, Garcia Garcia, Clara, Garcia Puig, Juan, Girbes Borras, Juan, Inigo Zaera, Pilar, Lopez de la Torre, Mart-n, Martinez Alfaro, Baldomera, Morales Portillo, Cristobal, Romero Sanchez, Paloma, Sebastian Ochoa, Nerea, Serrano Olmedo, Isabel, Tinahones Madueno, Francisco, Torres Jimenez, Rosa, Adeyemo, A. O., Bassa, Ayesha, Bhorat, A., Bhorat, Qasim, Blacking, Laura, Burgess, Lesley, Coetzee, Kathleen, Conradie, Hillet, Cyster, Henry, Distiller, Larry, Ellis, G. C., Gani, Mashra, Gordon, Debra, Govender, Parimala, Govender, Thirumani, Govender, Vimladhevi, Jivan, Daksha, Joffe, Barry, Jooma, Yaseer, Kaplan, Hilton, Komati, Stephanus, Kramer, Brian, Kruger, Sieglinde, Landau, Stanley, Latiff, Gulam, Maritz, L., Matthews, Peter, Middlemost, S. J., Ngcakani, Nomangesi, Nortje, Hennie, Osman, Yasmin, Padayachee, Trevenesan, Podgorski, Gracjan, Potts, Jenny, Pretorius, Catharina, Prozesky, Hans, Snyman, Hans, Tayob, Mohammed, Urbach, Dorothea, van der Merwe, Maryke, Vorajee, Haroon, Wilson, Nadine, Wing, J. R., Lee, Jie Eun, Ahn, Chang Ho, Kim, Nam Hoon, Kim, Sun Hwa, Hwangbo, Yul, Ko, Sun Hye, An, Jee Hyun, Ko, Seung Hyun, Lee, Ji Hyun, Noh, Jung Hyun, Ji, Myeong Jin, Kim, Kyeong Jin, Jung, Chan-Hyeon, Kim, DongJun, Kim, Kyongyoung, Kim, Lee-Kyung, Kim, SinGon, Kim, Eun Ky, Lee, Dong-Hwa, Cho, Young Min, Moon, Shin-Je, Oh, Chang-Myung, Hong, A. Ram, Park, Kyeong Seon, Yun, Jae Seung, Hong, Jae Won, Kim, Hee Young, Buranapin, Supawan, Deerochanawong, Chaicharn, Hengjeerajarus, Natavuth, Kosachunhanun, Natapong, Kuanprasert, Srun, Kunavisarut, Tada, Laortanakul, Rungnapa, Mangklabruks, Ampica, Phornphutkul, Mattabhorn, Prasitdamrong, Hutsaya, Snabboon, Thiti, Sriwijitkamol, Apiradee, Suwanwalaikorn, Sompongse, Tantiwong, Puntip, Tejavanija, Sirakarn, Vorasettakarnkit, Yongkasem, Alasabbagh, Samer, Bagais, Christos, Bingley, Polly, Borthwick, Les, Brett, Barbara, Davidson, Sue, Ewing, Jane, Garesse, Robert, Gillani, Syed, Gkastaris, Konstantinos, Herring, Roselle, Illsley, Graham, Johnson, Andrew, Kaplan, Felicity, Lonnen, Kathryn, Malcolm, Ellen, McCrimmon, Rory, Mcknight, John, Nair, Rajiv, Patel, Vinod, Pearson, Ewan, Raghavan, Rajeev, Raj, Suchitra, Russell-Jones, David, Sampson, Mike, Singh, Baldev, Sukamer, Nithya, Turner, Jeremy, Venkataraman, Hema, Viljoen, Adie, Wake, Deborah, Barnes, Cassandra, Boyd, Gary, Childress, Gwen, Coleman, Debora, Combs, Judy, Davis, Leon, Davison, Kentress, DeAtkine, David, Dunaway, Linda, Duncan, Janet, Hibbard, Nina, Martin, Melissa, Nichols, Melissa, Painter, Karolynn, Perkins, Tammy, Quinney, Rosylen, Raymond, Katrina, Roney, Christopher, Sanchez, Gilberto, Sosnowchik, James, Sultan, Farah, Talley, Shellie, Trippe, Bruce, Tuck, Pamela, Vaughan, T., Warriner, Amy, Watts, Tamara, Williams, Hayes, Abidov, Aiden, Abidov, Yulia, Anderson, Corey, Avila, Vanessa, Baraniak, James, Berry, Barbara, Bessette, Lynn, Blackwell, Gina, Burrows, Jennifer, Caldron, Meghan, Chang, Chui-An, Collins, Elizabeth, Crawford, Meli'sa, Delfin, Katherine, De'Loera, Jessie, Dokken, Betsy, Feld, Lawrence, Gill, Ryan, Gordon, James, Gordon, Rachel, Gullick, Nicole, Gutierrez, Diane, Harrison, Larissa, Haught, Annamarie, Hemmila, Karin, Hendrickson, Darell, Horsley, Craig, Hsu, Connie, Jerrell, Maggie, Kertesz, Briana, Khananisho, Paulina, Lenzmeier, Sonia, Lenzmeier, Thomas, Lipschitz, Barbara, Lonquist, Mark, Mather, Dana, (Shelley) Miceli, Michelene, Norris, Gwenth, Padilla, Ann Marie, Petersen, Dena, Riffer, Ernie, Scott, Susan, Sheridan, Kathryn, Smith, Misty, Stump, Craig, Thomson, Stephen, Torok, Ernese, Vesely, Kelly, Vincent, Tom, Wilson, Christy, Wilson, Sandra, Agarwal, Monica, Appleberry, Kady, Barden, M. Gregg, Brickell, Lorrie, Bravo, Eric, Cassis, Cady, Covington, Becky, Devine, De'Andrea, Dishongh, Katherine, Dugger, Joseph, Evans, Lauren, Francis, Spencer, Johnson, David, Koneru, Kalyana, Kurck, Sheryl, Lingisetty, Chandra, Menke, Jennifer, Miller, Beatrice, Montgomery, Cristal, Nimmo, Teresa, Pace, Daniel, Pellegrino, Richard, Rose, Joseph, Straub, Karl, Stubbs, Amanda, Thomas, Leslie, Thrasher, James, Thrasher, Lesa, Wijewardane, Priyantha, Williamson, Kimberly, Acevedo, Lizeth, Ahmad, Aakif, Andresen, Teri, Anderson-Berman, Nancy, Ayele, Etsegenet, Baker, Janice, Banares, Arlene, Barsalou, Thea, Becker, Steven, Benavidez, JoAnn, Benitez, Guadalupe, Bernstein, Richard, Bhasker, Kala, Blain, Arthur, Blustin, Joy, Bughi, Stephanie, Carney, Kimberly, Castro, Gerardo, Catangay, Jennifer, Chambers, Joseph, Chan, Eve, Chang, Amy, Chang, Anna, Chavous Jr., Donald, Chen, Constance, Chiu, Ken, Chochinov, Ronald, Chu, James, Cleghorn, Monica, Cohen-Gadol, Shariar, Cokely, David, Collins, Michelle, Collins, Yolanda, Colomy, Carissa, Cruz-Corona, Yolanda, Cunnea, Virginia, Dailey, George, Dang, Andy, Dang, Trinh, De La Luz, Mabel, Delgadillo, Rico, Delgado, Michael, Desta, Taddese, Doriguzzi, David, Dulgeroff, Anthony, Einhorn, Daniel, Emery, Pamela, Figueroa, Martin, Fink, Raymond, Flowe, Chelsea, Flowers, Francesca, Fregosi, Julie, Garcia, Gabriel, Garcia, Maria, Gaudiani, Linda, Gawad, Michael, Ghattas, Sam, Gilroy, Christine, Gonzalez, Viviana, Gonzalez, Yadira, Guadron-Hernandez, Liliana, Ha, Thu, Haas, Terry, Harbison, Judy, Hernandez, Graciela, Hernandez, Robert, Herrera, Nancy, Ho, Vincent, Hsu, Kang, Humphries, Denise, Huynh, Vincent, Jacobs, Shahram, Jardula, Michael, Jarman, Cheryl, Kabongo, Martin, Kafri, Hassan, Kaplan, Roy, Kim, Grace, Kobayashi, Gary, Korff, Gary, Kowalick, Alexandra, Levin, Ellis, Lewis, Erin, Lisovskiy, Svetlana, Luu, Hieu, Malkhassian, Daniel, Maletz, Louis, Martinez, Geraldine, Martinez, Gilbert, Martinez-Miss, Salomon, McCallum, James, Melikian, George, Metcalf, Francine, Michlin, Bernard, Michlin, Shira, Mitchell, Anitha, Moattari, Ali Reza, Montano-Pereira, Cynthia, Moon, Mia, Naderi, Bahar, Nagata, Jenna, Nguyen, Christopher, Norwood, Paul, Garcia, Sagrario Olmos, Olsen, Sharon, Pardino, Aarika, Parkes, Kathleen, Pascal, Aileen, Patel, Mihir, Paulson, Carolyn, Pernia, Kay, Perez, Marisol, Pham, David, Presant, Larry, Preston, Krista, Reeves, Laurie, Richards, Jessica, Rios-Santiago, Jessica, Risser, Joseph, Rodriguez, Silvia, (Cherrie) Rosal, Rosario, Rosenblit, Paul, Rosero, Raquel, Sadler, Chris, Samoa, Raynald, Sanchez, Liliana, Schaeffer, Cynthia, Schwartz, Alan, Scott, Christopher, Scott, Courtney, Scott, Cranford, Shartel, Jo-Ann, Shaw, Sylvia, Sivalingam, Kanagaratnam, Sligh, Scott, Sligh, Teresa, Smith, Bradley, Soler, Daniel, Spencer, Torre, Stalters, Sophia, Stone, Jenine, Szlachcic, Yaga, Thorsell, Ashley, Tu, Zhongheng, Unger, Jeffrey, Vela, Teresa, Walton, Anita, Whittle, Jessica, Wilson, Lou Ellen, Wing, Zandra, Wright, Philippa, Wyman, Shannan, Yao, Ni, Zlock, Douglas, Baker, Chelsea, Bakkum, Robyn, Bird, C. David, Carangi, Gwen, Cohen, Kenneth, Daza-Taylor, Kristen, Diesburg-Stanwood, Amy, Douglass, Sara, Finck, Lani, Karaboitis, Krisoula, Kerstein, Howard, Lesh, Kurt, Loesch, Ryan, McClure, Lori, Nevarez, Max, Pavol, Bristol, Rasouli, Neda, Rockler, Briana, Sanagorski, Rebecca, Solano, Royce, Underkofler, Chantal, Van Winkle, Rebecca, Weiss, Sarah, White, Katherine, Wirtemburg, Patricia, Zarrabi, Lida, Zemel, Leonard, Barchini, George, Casagni, Kimberely, Cordisco, Marie Elena, Davis, Amanda, Duffy-Hidalgo, Bobbi, Huntley, Richard, McNicol, Donald, Miller, Neil, Mukwaya, Margaret, Northrup, Patricia, Platt, Jonathan, Rabideau, Diane, Randolph, Pamela, Rose, Suzanne, Samuel, James, Savino, Robert, Soufer, Joseph, Torello, Carole, Abinader, Azarel, Agosto, Milagos, Aguirre, Frank, Alexander, Lori, Almanza, Orlando, Alvarez, Dalia, Anees, Muhammad, Aqua, Keith, Arazo, Luz, Asberry, Claudia, Ashley, Alyssa, Balentine, Tracy, Barta, Melissa, Bertot, Ivan, Binns-Leon, Michelle, Borello, Nora, Bostick, Janette, Boucher, Loria, Braddy, Dalton, Breton, Cristian, Broxton, Bridgitte, Burke, Deborah, Cabielles, Tania, Calderon, Juan, Canaan, Yamil, Canelon, Gustavo, Cardona, Jose, Castillo-Gonzalez, Sheila, Castro, Kenia, Chacon, Jessica, Chehade, Joe, Church, Lara, Cohen, Lisa, Crews, Erin, Cromer, Carol, Cromer, Michael, Cuello, Jorge, Cusi, Kenneth, de Leon, Karel, Delgado, Edmund, Delima, Selma, Denson, Janneral, DeVries, Benjamin, Diaz, Maritza, Digon, Beningo, Dowell, Michelle, Dunn, Kelly, Ellington, Dickson, Emerick, George, Encarnacion, Frances, Ezell, Leslie, Fahmie, Ashley, Fernandez, Noel, Figueredo, Rommel, Flores, Patricia, Fonseca, Juan, Freeman, Alain, Freeman, Erica, Frias, Juan, Garcia, Lazaro, Geronilla, Giovanni, Hamilton, Maxine, Hanabergh, Rodolfo, Hanson, Lenita, Harris, Kim, Hasan, Syed, Hendrick, Mary, Hicks, Melissa, Hoffman, Lara, Holt, Antoniwa, Hutchinson, Rachel, Iparraguirre, Harold, Janicka, Ania, Janovitz, Richard, Jones, Dawn, Jones, Sarah, Kaplun, Polina, Kelijman, Mirtha, Kersey, Angela, Khan, Ashraf, Khan, Misal, Kirk, Gregory, Konwai, Ada, Kovar, Meghan, Kutner, Mark, Lafaille, Jimmy, Leach, Dana, Levenson, David, Lewy-Alterbaum, Lorena, Light, Timothy, Lo, Margaret, Loman, Lusiana, Long, Sarah, Love, Jeremy, Madera, Arelis, Magee, James, Mallitz, Michelle, Marquez, Farid, Marshall, Richard, Mary, James, Mateu, Janet, McKenzie, Leanna, McKenzie, Rona, McKenzie, Wilfred, Mendelson, Reina, Mendez, Janet, Merlos, Ledis, Mierau, Jennifer, Miller, Robert, Miranda-Palma, Bresta, Montoya, Carla, Navarro, Eduardo, Neller, Christian, Nossa, Janette, Osborn, Tracey, Patel, Bijal, Penabad, Jesus, Perez, Gilberto, Pineda, Daniel, Pinero-Pilona, Antonio, Platt, George, Prestwood, Elfrida, Quintero, Luis, Rengifo, Rodney, Reyes, Dannier, Rivas, Aolani, Rivero, Mileydis, Robinson, Sonya, Robison, Dawn, Rodriguez, Dalier, Rodriguez, Ivete, Rodriguez, Toni, Rosario, Cristobal, Rosenwasser, Rebecca, Roura, Miguel, Schramm, Erich, Schramm, Rashi, Schweppe, Laurie, Segel, Scott, Sepulveda, Maria, Sheets, Lori, Shields, Karen, Smith, Krystal, Smith, Meridith, Somerstein, Claudia, Solano, Maria, Suarez, Manuel, Suarez, Omar, Suarez, Rogelio, Suarez, Victor, Sultan, Senan, Sutton, David, Szilagyi, Istvan, Thorne, Margaret, Travaglini, Stefano, Trevino, Miguel, Uriarte, Oscar, Vizcaino, Luis, Wadud, Khurram, Wehmeier, Kent, Weinstein, Debra, Welch, Celeste, White, Alexander, White, Basil, Williams, Tammy, Williamson, Cathi, Zwick, Lisa, Adams, Cynthia, Arkin, David, Bode, Bruce, Bonner, Sheila, Bonner, Wes, Bowen, Danielle, Bradley, Brooke, Bradley, Paul, Brennan, Elizaebeth, Brown, Cynthia, Brown, De'Aira, Burgess, Elizabeth, Collett, Taryn, Cook, Jennifer, Corse, Steven, Dukes, Kaitlyn, Durrence, Jenna, Dutton, Robin, Estes, Susie, Falcone, Laura, Gaskin, Katherine, Goswami, Ketan, Hart, Mari, Jester, Donni, Kies, Staci, Leiker, Abigail, Lu, Peter, Mahakala, Aparna, Maher, Maxine, Miller, Alan, Miller, Todd, Munoz, Miguel, Musto, Michele, Odugbesan, Adeniyi, Olson, Darin, Osborn, Nicole, Pace, Kerri, Pajkovic, Gordana, Paulus, Carolyn, Phillips, Lawrence, Reddick, William, Reed, John, Rowe, Shasta, Sadler, Barney, Sapp, Tabby, Savoye, Louise, Shore, David, Shuman, Susan, Sittle, Jessica, Standard, Shana, Wardell, Karla, Workman, Amy, Carreira, Tabitha, Fitz-Patrick, David, Hean, Vutheary, Limcolioc, April, Nihei, Megan, Park, Youngmee, Pau, Cindy, Shannon, Lindsey, Trotter, Alanna, Williams, Sierra, Coughenour, Tiffany, Liljenquist, John, Vance, Carl, Williams, Jonathan, Agaiby, Eva, Agaiby, John, Argo, Kelly, Azad, Nasrin, Backus, Arnetta, Bartlett, Andrew, Bellucci-Jackson, Jennifer, Boncu, Otilia, Brodt, Pamela, Carlson, Hope, Collins, Kathleen, Delibasic, Maja, Dor, Isaac, Dukett, Mary, Emanuele, Nicholas, Gabel, Faith, Giardino, Alexandra, Hoelzer, David, Hsieh, Annming, Jayaramaiah, Poornima, Kearney, Tracy, Kelley, Kathleen, Kravarusic, Jelena, Lawless, Andrea, Maheshwari, Hiralal, Martin, Elonia, McCall, Linda, Mikell, Frank, Nallala, Deepika, Said, Sufyan, Sakla, Nadia, Schiferi, Joanna, Smith, Patricia, Stokes, John, Sugimoto, Danny, Sugimoto, Michael, Swan, Delores, Alfata, Sarab, Beavins, Jill, Bogardus, Christine, Bogardus, Donald, Calvert, Brittany, Calvin, Krystle, Carlton, Kristin, Condit, Jonathan, Cornett, George, Covert, Carissa, Dela Llana, Alexander, Dixon, Rosie, Felker, Dean, Fogle, Sara, Harris, Leslie, Hoebeke, Roberta E., Silva, Ricardo, Johnson, Tabitha, Johnston, Kelly, King, Jennifer, Lang, Amber, Maynard, Kenneth, McDaniel, Vickie, McGrath, Caitlin, Moretto, Thomas, Ndukwu, Ikeadi, O'Connor, Leo, O'Connor, Thomas, Oliver, Tonya, Overmars, Stephanie, Patel, Minesh, Patterson, Geraldine, Powell, Talessa, Raphael, Annmarie, Raphael, Rod, Reedy, Mark, Reyes, Hubert S., Ridge, Terry, Rutherford, Mary S., Sebastian, Mike, Shaeffer, Laura, Sheets, Michelle, Thomas, Karen, Trueblood, Nancy, Tucker, Tiffany, White, Adrian, Wooldridge, Evan, Wright, Alison, Zapinski, Dawn, Cieloha, Megan, Coker, Clarine, Fletcher, Cherisa, Kay, Jennifer, Larsen, Katelyn, Marar, Isam, Motz, Zachary, Paul, Jamie, Pokorski, Alan, Rabadi-Marar, Diana, Scheideler, Kylie, Sobczyk, Jill, Sweeney, Kolbie, Brink, Nathalie, Buth, Dennis, Grimes, Katlyn, Lakin, Gregory, Loewen, Barbara, Secrist, Neal, Simon, William, Steere, Diane, Talbot, Kimberly, Wheeler, Christina, Adams, Derick, Armour, Wilhelmina, Asher, Whitney, Bays, Harold, Behl, Noreen, Conn, Brittany, Dye, Lyndsey, Earl, Jennifer, Farris, Neil, Figueroa, Sergio, Fruit, Olivia, Hobbs, Coury, Howard, Kristen, Jackson, Tamara, Kain, Angela, Karounos, Chrisi, Keiran, Sarah, Kennedy, Ryan, King, Kara, Krishnasamy, Sathya, Lambdin, Winona, Micklewright, Gezina, Mokshagundam, Sri, Mooney, Stephen, Moore, Melanie, Morgan, Denise, Morley, Robert, Newsome, Stacy, Nichols, Jennifer, Nims, Diana, Nockerts, Nichole, Oremus, Ruth, Ritchey, Barbara Michelle, Shelton, Christina, Smith, Danielle, Walker, Debra, Weiter, Kathleen, Whitehead, Rebecca, Wood, Robert, Woodruff, Robin, Young, J. DeShay, Alper, Arnold, Berry, Martha, Gauthier, Nadine, Griffin, Catina, Haynes, Elvia, Lawrence, Jereta, McCormack, Teraina (Terry), Midyett, Catherine, Rangaraj, Uma, Smith, William, Stricker, Makenzie, Tandron, Ileana, Vargas, Ramon, Wagner, Michele, Albert, Marie, Baillargeon, Gail, Stephens, John, Aroda, Vanita, Dempsey, Michael, Junker, Herman, Lopez, Meyling, Shepard, Marc, Ciccarelli, Carol, Datu, Joycelyn, Gallagher-Dorval, Karen, Hartigan, Celia, Kowaloff, Edward, Lock, John-Paul, Rosano, Nina, Shaw, Bernadette, Thompson, Michael, Abbo, Camerin, Anton, Salwan, Baker, Lydia, Bhan, Arti, Blackmer, Karla, Boley, Bryon, Hyde, Desirae, Bonema, John, Carlin, Tamara, Curran, Nancy, Dandois, Bethani, Dermyer, Abigail, Dubeck, Janet, Elkins, Jennifer, Ferris, Pamela, Fraser, Neil, Kozma, Julia Gargan, Gasparovich, David, Grodman, Robert, Hampson, Jaison, Hewitt, Mitzie, Hiatt, Judy, Hopkins, Ashley, Howard, Jennifer, Joliat, John, Joliat, Jonathan, Kalt, Steven, Katzman, Steven, Kogelman, Jesse, Kruger, Davida, Kurkowski, April, Lambert, Jodi, Levcovici, Elisabeta, Lockwood, Karen, Lumberg, Michael, McMullen, Lindsay, Meyers, Peter, Minto, Carrie, Nelson, Tina, Neuner, Gregory, Nurmi, Kevin, Perkins, Judy, Plunkett, Cynthia, Ruoff, Gary, Samantray, Julie, Sawah, Ahmed, Secord, Samantha, Seyoum, Berhane, Sherman, Sarah, Simpson, Michael, Sinkoff, Mark, Skoney, Joseph, Small, Jami, Szerlong, Heidi, Tinetti, Timothy, Toomey, Adam, VanDerWerff, Holly, Whitehouse, Fred, Wilkins, Raechelle, Wolf, Stephanie, Yarows, Steven, Eldred, Edward, Hester, Kim, Huling, Randall, Moore, Kerry, Preslar, Kristina, Proge, Nakia, Smith, Lora, Young, Gerri, Bybee, Kevin, Carr, George, Case, Christopher, Forker, Alan, Goeke, Lindsay, Kocher, Darlene, Lin, Oscar, Littlefield, James, Mendoza, Robinson, Moore, Michelle, Oberhaus, Barbara, Reed, Larry, Rutherford, Cheryl, Windsor, Sheryl, Ackerman, Kim, Christensen, Reed, De Souza, Jose, Douglas, Kirsten, Hrncirik, Therese, Lefkowicz, Magen, McDonnell, Lindsey, Severa, Larry, Tjaden, Jeffrey, Ward, Laura, Addison, Shayla, Anderson, Robert, Baker, Claire, Baum, Robert, Belitz, Jenny, Boerner, Shannon, Desouza, Cyrus, Drincic, Andjela, Fitzgibbons, William, Francis, Jessica, Garvin, Maureen, Goldner, Whitney, Goodrich, Melissa, Grubbs, Lisa, Hatcher, Theresa, Hochstein, Renee, Hunter, Christine, Keuchel, Janet, Konigsberg, Sarah, Kuechenmeister, Lisa, Mack, Lynn, McKnight, Thomas, Mensik, Hanna, Mitchell, Jan, Moeller, Jennifer, Montanez, Edward, Montoya, Paul, Nemecek, Tiffany, Neumeister, Amy, Newcomb, Jefferey, Pracht, Shelby, Radke, Kaitlin, Rahman, Jennifer, Renter, Samantha, Reynolds, Jill, Grace Rodriguez, Maria, Satorie, Jessica, Schiermann, Lynnda, Severson, Megan, Shivaswamy, Vijay, Snyder, Janice, Tillson, Renee, Vasey, Andrew, Wahl, Timothy, Weeks, William, Wolf, Thomas, Springer, Brian, Mitchell, Janice, Woodruff, Mark, Alvarez, Isis, Bowers, Rachel, Cala-Anaya, Franklin, Castellanos-Rodriguez, Rudiber, Christopher, Janice, Concepcion, Gelvis, Fernandez, Dareana, Ghanem, Paula, Harmon, Nicolette, Kaiser, Heather, Kaplan, Westbrook, Klugh, Serena, Le, Nicholas, Lehrner, Stephanie, Lopez, Robert, Martin, Olga, Martinez, Tina, Martini, Nicole, Molin, Clifford, Nakhle, Samer, Newsome, Yvonne, Neylon, Ellen, Olsen, Jarvis, Palal, Betsy, Philander, Peter, Rosario, Adriana Ruiz, Sanchez, Mary, Sierra-Garcia, Miguel, Smith, Myesha, Trenche, Samuel, Trippi, Danna, Vernetti, Nicholas, Villegas, Laura, White, Briana, Wilcox, Simmon, Carmolli-Cornette, Lisa, Chuang, Ellie, Hoffman, Sheila, Laliberte, Alison, Marshall, Lisa, Meroski, Pamela, O'Neil, Christine, Shippey, Jeanette, Spector, Linda, Cam, Jenny, Chen, Tina, Damle, Jagadish, Holman, Rebecca, Liu, Jenny, Milazzo, Carmelo, Quach, Brenda, Yang, Bin, Ahmad, Basharat, Aro, Dominic, Azeem, Fouzal, Bonaccorso, Antoinette, Brancato, Lenore, Brautigam, Donald, Charatz, Seth, Chiarot, June, Cunningham, Linda, DiCerbo, Nancy, DiGiovanna, Michael, Dluge-Aungst, Dawn, Dolbeer, Traci, Donovan, Daniel, Duma, Carol, Ellwood, Rebecca, Freedman, Zachary, Gorman, Timothy, Gunther, David, Hogan, Eileen, Hoffman, Lisa, Kapoor, Anoop, Kelly, Michelle, Kitchen, Timothy, Lam, David, Levister, Camilla, Levy, Carol, Lopez, Carlos, Lyons-Patterson, Jane, Makam, Sashi, Mauceri, Diana, McClary, Carole, Murak, Daniel, Nolan, Kelly, Nunez, Carlos, Elliott, Theresa Ohlson, Ostrowski, Phillip, Pallai, Ajish, Porges, Andrew, Rodes, Alfredo, Rosenberg, Richard, Rubel, Lance, Serrano, Lelanie, Shannon, Daniel, Sinha, Rabi, Snyder, Brian, Sy, Claude, Tang, Rocky, Varavenkataraman, Raghupathy, Winterberger, Amy, Allen, Stacy, Anderson, Marshall, Asbill, Mark, Beasley, Amanda, Bennett, Chrisitian, Bergamo, Katherine, Bilbro, Scott, Brannock, Sarah, Brown, Laura, Bryant, Danielle, Buck, Genena, Burdette, Tara, Buse, John, Butler, Laura, Caldwell, Ronald, Cannon, Daniel, Cannon, Kevin, Carter, Casey, Cherry, Amanda, Comer, Zoe, Crittenden, Susan, Cuffee, 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Cloud, Mark, Cohen, A. Jay, Coulter, Alice, Dotson, Kimberly, Green, Christopher, Helton, Ashley, Houstrup, Jody, Huffman, David, Hurst, Fred, Hurst, James, Jantzi, Curtis, Jerkins, Randy, Jerkins, Terri, Jones, Mandy, Kelley, Shane, Kroulek, Judy, Lawhun, Dennis, Lee, Marcus, Louthan, James, Manning, Rickey, May, Michael, Means, Katherine, Monroe, Jeanabe, Morawski, Emily, Morin, David, Morris, Barbara, Murray, John, Nichols, Robert, Olivi, Stacie, Pennington, Kristina, Poe, Jenny, Pour, Omid Rad, Reeves, Michael, Reeves, Pamela, Root, Connie, Rose, Karen, Rutledge, Lily, Ryan, Eugene, Schwartz, Patricia, Shafer, Jennifer, Singh, Chitra, Smith, Ashley, Snow, Rodney, Stamps, Henry, Staton, Peggy, Stevens, Jeffrey, Stovall, Cathy, Sturgeon, Rodney, Tapp, John, Tapp, Stacy, Warner, Carla, Weiss, Melissa, White, Judith, Wierum, Craig, Williams, Konya, Wright, Tiffanie, Abreu, Marconi, Agarwal, Vandana, Ahmad, Aftab, Ahmad, Asma, Ahmed, Faiz, Ahn, Lily, Alaoui, Rachid, Alarcon, Stephanie, Allison, Dale, 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Eizensmits, Christina, Espinosa, Valerie, Evans, Charles, Frisinger, Cathy, Ganta, Shylesh, Galtney, Kirsten, Gammon, John, Garcia, Analisa Marie, Garcia, Ronald, Glaspie, Tina, Golici, Laura, Gonzalez, Julian, Grant, David, Green, Carrie, Groce, Lindsay, Guevara, Stephanie, Gutierrez, Mary, Hance, Cortney, Harden, Tiffany, Harrison, Lindsay, Herrera, Carlos, Hettler, Evelyn, Holcomb, Michelle, Hoste, Laura, Hudson, Tina, Huerta, Leticia, Jain, Mahendra, Jayaram, Preeth, Johnson, Monique, Johnson, Olivia, Jones, Laurie, Joseph, John, Juarez, Misty, Karimjee, Najmuddin, Kephart, Ashley, Khan, Armgan, Khan, Jalil, Killian, Michael, Kniffen, Wendy, Koops, Maureen, Kwan, Louise, La, John, Laabs, Jessica, Ledesma, Gilbert, Lee, Monica, Leuck, Kathryn, Livingston, Carrie, Llanas, Teresa, Longoria, Andy, Lorta, Jesse, Lothringer, Larry, MacAdams, Maria, MacAdams, Michael, MacGillivray, Brian, Mageno, Melissa, Malek, Megan, Manley, Meghan, Marler, Karen, Martinez, Cristina, Massie, Jodi, Mateos, Glenda, Mathew, Reena, Maya, Claudia, Mazour, Meg, Mbogua, Caroline, McClendon, Robert, McMullen, Deirdre, Meisner, Carl, Menchaca, Ethelina, Meyers, Linda, Miklius, Audrey, Milam, Alissa, Milam, Ronnie, Miller, Tracey, Mize, Lisa, Moczygemba, Roger, Nafegar, Alexandria, Naidu, Jayaram, Nair, Archana, Nguyen, Alison, Nielsen, Douglas, Nisnisan, Josier, Nisnisan, Maria, Oden, Wendy, Orsak, Jessica, Ozer, Kerem, Papacostea, Olivia, Panchal, Ravi, Parikh, Manish, Parthiban, Beneta, Perrin, Brittney, Perkins, Harvonya, Poduri, Madhuri, Pop, Laurentiu, Portales, Nancy, Porter-Tucci, Linda, Postell, Sharon, Pucillo, Ronald, Reddy, Madhavi, Reddy, Rajneesh, Almodovar, Ramon Gilberto Reyes, Richard, Timiki, Richardson, Michele, Riesch, Louie, Rivera-Flores, Samuel, Rizvi, Abid, Rizvi, Samana, Rodas, Kristen, Rodgers, Mark, Roe, Erin, Rogers, Rebecca, Romero, Reina, Rooker-Morris, Leslie, Rosenstock, Julio, Sachson, Richard, Salcedo, Alfredo, Schill, Joseph, Schuh, Kristy, Schuster, 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Algus, Michael, Gilbert, Matthew, Gorson, David, Marney, Annis, Rodriguez, Juan Pablo Perdomo, Roth, Marilynn, Scofield, Sheilah, Thottan, Anna, Bittorf, Margaret, Botros, Emad, Carpenter, Jeanette, Dashiell, Carie, Dimascio-Johnson, Nancy, Fredrickson, Sonja, Gruenther, M., Hall, Lisa, Hartman, Aaron, Hiner, Janette, Kelley, Donna, Kimmel, Melissa, Larrick, Laura, Lawson, Marie, Levy, James, Lewis, Teneshia, Lovell, Charles, Newby, James, Nichols, Michelle, O'Donnell, Philip, Orengo, Sheyla, Pecsok, Thomas, Reiss, Lind, Tarkington, Phillip, Yeatts, Donald, Zieve, Franklin, Ahmed, Imtiaz, Ali, Sajid, Anwar, Sami, Cathcart, Harold, Dawson, Lucia, Floresca, Rolando, Galvan, Ashley, Gardner, Timothy, Halsey, Kami, Hashmi, Farrukh, Hegel, Jackie, Landon, Megan, Moulton, Katlynn, Nand, Cheta, Sakic, Amra, Sevey, Brandie, Wilson, Bruce, Ahl, Scott, Blank, Robert, Coly, Gerard, Hoenig, Jennifer, Jain, Rajeev, Joseph, Elizabeth, Kasprzak, Debra, Kisiel, Lalaine, Maaske, Maurene, Manadhar, Smriti, Patel, Shailendra, Sickler, Whitney, Grp, D.E.V.O.T.E. Study, Acibadem University Dspace, Marso S.P., Mcguire D.K., Zinman B., Poulter N.R., Emerson S.S., Pieber T.R., Pratley R.E., Haahr P.-M., Lange M., Brown-Frandsen K., Moses A., Skibsted S., Kvist K., Buse J.B., and Buscemi S
Subjects: Insulin degludec, Blood Glucose, Male, medicine.medical_treatment, DEVOTE Study Group, Insulin Glargine, Type 2 diabetes, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, diabetes, insulin, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, GLUCOSE CONTROL, 11 Medical and Health Sciences, RISK, COMPLICATIONS, OUTCOMES, Incidence, General Medicine, Middle Aged, Insulin, Long-Acting, VARIABILITY, Cardiovascular Diseases, diabetes mellitus, Female, Life Sciences & Biomedicine, Human, medicine.drug, medicine.medical_specialty, 030209 endocrinology & metabolism, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Humans, Hypoglycemia, Hypoglycemic Agents, Medicine (all), Bedtime, Article, EVENTS, 03 medical and health sciences, HYPOGLYCEMIA, Medicine, General & Internal, Internal medicine, Diabetes mellitus, General & Internal Medicine, medicine, Intensive care medicine, METAANALYSIS, Science & Technology, Hypoglycemic Agent, Insulin glargine, business.industry, Insulin, medicine.disease, business, BASAL INSULIN
Abstract: BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P
Published: 2017

20. Liraglutide and cardiovascular outcomes in type 2 diabetes

Author: Robert Cuddihy, Rebeca Reyes-Garcia, Eduardo Hernández Salazar, Pawel Bogdanski, Tanja Milicic, Mihaela Vladu, Farida Valeeva, Silvio Buscemi, Veroniek Harbers, Thomas Pieber, Jeppe Gram, Martin Haluzik, Søren Gregersen, Ismet Tamer, Prasad Gunasekaran, Jean O'Connell, Peter Lommer Kristensen, Mustafa Kemal BALCI, Robert Lindsay, Hans Prozesky, JOSE ITALO MOTA, Dilek Gogas Yavuz, Pavel Trachta, Katerina Anderlova, Lise Tarnow, Paramesh S, Miguel Camafort-Babkowski, Selcuk Dagdelen, Shu-Fu Lin, Jarmila Krizova, İSMAİL ENGİN, Marcin Kunecki, Renan Montenegro Junior, Hayriye Esra Ataoglu, IREM DINÇER, John Buse, Jose Sgarbi, Christopher Gilfillan, Tatiana Kiseleva, Henna Cederberg, Sadi Ozdem, Chung-Huei Huang, Miljanka Vuksanovic, Sten Madsbad, Milan Piya, Patrick English, Yu-Yao Huang, Monika Zurawska-Klis, Alan Jaap, Alessandro Mattina, MARIANNA MARANGHI, Yazıcı, Dilek, Marso, S. P., Daniels, G. H, Brown-Frandsen, K., Kristensen, P., Mann, J, F., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, R., Ravn, L. S., Steinberg, W. M., Stockner, M., Zinman, B., Bergenstal, R. M, Buse, J. B., LEADER Steering Committee, LEADER Trial Investigators, School of Medicine, Department of Endocrinology, Diabetes and Metabolism Diseases, Marso, S., Daniels, G., Frandsen, K., Mann, J., Nauck, M., Nissen, S., Poulter, N., Ravn, L., Steinberg, W., Bergenstal, R., Buse, J., Bergenstal R, Buse J, Daniels G, Mann J, O, Buscemi, S., et al, Marso, Steven P., Daniels, Gilbert H., Kirstine Brown Frandsen, Peter, Kristensen, Mann, Johannes F. E., Nauck, Michael A., Nissen, Steven E., Stuart, Pocock, Poulter, Neil R., Ravn, Lasse S., Steinberg, William M., Mette, Stockner, Bernard, Zinman, Bergenstal, Richard M., Buse, John B., for the LEADER Steering Committee on behalf of the LEADER Trial Investigators [Study Investigator:, . . ., Gambineri, Alessandra, Repaci, Andrea, Ribichini, Danilo, ], . ., National Institute for Health Research, and Imperial College Healthcare NHS Trust- BRC Funding
Subjects: Male, Gastrointestinal Diseases, Treatment outcome, Clinical Biochemistry, Myocardial Infarction, Type 2 diabetes, 030204 cardiovascular system & hematology, law.invention, Medicine, Endocrinology, 0302 clinical medicine, Randomized controlled trial, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Liraglutide, Middle Aged, Stroke, Treatment Outcome, Medicine (all), law, Cardiovascular Disease, Clinical-trial, Pancreatitis, Therapies, Cancer, Drugs, 11 Medical and Health Sciences, Research Support, Non-U.S. Gov't, PANCREATITIS, Hazard ratio, LEADER Steering Committee, Follow up studies, General Medicine, Albiglutide, Multicenter Study, TRIALS, Randomized Controlled Trial, Life Sciences & Biomedicine, Cardiovascular outcomes, medicine.drug, Human, medicine.medical_specialty, Gastrointestinal Disease, MEDLINE, 030209 endocrinology & metabolism, LEADER Trial Investigators, Placebo, Follow-Up Studie, 03 medical and health sciences, Medicine, General & Internal, Research Support, N.I.H., Extramural, General & Internal Medicine, Diabetes mellitus, Internal medicine, medicine, Journal Article, Glycemic efficacy, Science & Technology, Hypoglycemic Agent, business.industry, Semaglutide, medicine.disease, Surgery, business, Follow-Up Studies
Abstract: The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P, Novo Nordisk; National Institutes of Health; LEADER ClinicalTrials.gov
Published: 2016

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20 results on '"Poulter, Neil R."'

1. Safety of Liraglutide in Type 2 Diabetes and Chronic Kidney Disease.

2. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure.

3. Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy: Evidence from the LEADER trial.

4. Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus.

5. Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10).

6. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke.

7. Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease: Results of the LEADER Trial.

8. Type 2 Diabetes and the Reduction of Cardiovascular Risk: Sorting Out the Actors and the Roles.

9. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis.

10. Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2).

11. Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal.

12. Liraglutide and Renal Outcomes in Type 2 Diabetes.

13. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.

14. Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) - DEVOTE 1.

15. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.

16. LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial.

17. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

18. Blood pressure and glucose control in subjects with diabetes: new analyses from ADVANCE.

19. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

20. Liraglutide and cardiovascular outcomes in type 2 diabetes

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