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1. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial.

Author

McGuire DK, Busui RP, Deanfield J, Inzucchi SE, Mann JFE, Marx N, Mulvagh SL, Poulter N, Engelmann MDM, Hovingh GK, Ripa MS, Gislum M, Brown-Frandsen K, and Buse JB

Subjects
Male, Humans, Aged, Hypoglycemic Agents adverse effects, Glucagon-Like Peptides adverse effects, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 chemically induced, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic chemically induced, Atherosclerosis complications, Atherosclerosis drug therapy, Atherosclerosis epidemiology, Coronary Artery Disease, Insulins
Abstract

Aim: To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants., Materials and Methods: In SOUL, the effects of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double-blind, parallel-group, placebo-controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m 2 ). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event-driven trial will continue until 1225 first adjudication-confirmed MACEs have occurred. Enrolment has been completed., Results: Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m 2 , glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium-glucose cotransporter-2 inhibitors (26.7%) and dipeptidyl peptidase-4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants., Conclusion: SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Published
2023
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2. Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics.

Author

Lingvay I, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lincoff AM, Marso SP, Fries TM, Plutzky J, and Ryan DH

Subjects
Female, Humans, Male, Middle Aged, Hypoglycemic Agents therapeutic use, Obesity complications, Obesity drug therapy, Obesity chemically induced, Overweight complications, Overweight drug therapy, Overweight chemically induced, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Cardiovascular Diseases chemically induced, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 diagnosis, Myocardial Infarction epidemiology, Myocardial Infarction prevention & control, Peripheral Arterial Disease chemically induced, Stroke
Abstract

Objective: This paper describes the baseline characteristics of the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) study, one of the largest cardiovascular (CV) outcome studies in the field of obesity, which evaluates the effect of semaglutide versus placebo on major CV events., Methods: SELECT enrolled individuals with overweight or obesity without diabetes, with prior myocardial infarction, stroke, and/or peripheral artery disease. This study reports participants' baseline characteristics in the full study population and subgroups defined by baseline glycated hemoglobin (HbA 1c ; <5.7%, ≥5.7 to <6.0%, ≥6.0 to <6.5%), baseline waist to height ratio tertile, and qualifying prior CV event or condition., Results: The study enrolled 17,605 participants (72.5% male) with an average (SD) age of 61.6 (8.9) years and BMI of 33.34 (5.04) kg/m 2 . The most common prior CV event was myocardial infarction (76.3% of participants), followed by stroke (23.3%) and peripheral artery disease (8.6%). Furthermore, 24.3% had a heart failure diagnosis. Two-thirds of participants (66%) had HbA 1c in the prediabetes range (5.7%-6.4%). Across groups of increasing HbA 1c , prevalence of all CV risk factors increased., Conclusions: The enrolled population in SELECT includes participants across a broad range of relevant risk categories. This will allow the study to garner information about the CV benefits of semaglutide across these relevant clinical subgroups., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Published
2023
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3. 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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4. 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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5. DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality.

Author

Pieber TR, Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pratley RE, Woo V, Heller S, Lange M, Brown-Frandsen K, Moses A, Barner Lekdorf J, Lehmann L, Kvist K, and Buse JB

Subjects
Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 mortality, Double-Blind Method, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemia metabolism, Hypoglycemia mortality, Hypoglycemic Agents therapeutic use, Insulin Glargine therapeutic use, Insulin, Long-Acting therapeutic use, Male, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemia drug therapy
Abstract

Aims/hypothesis: The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality., Methods: In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population., Results: There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA 1c , BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group., Conclusions/interpretation: The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect., Trial Registration: ClinicalTrials.gov NCT01959529.

Published
2018
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6. 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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7. 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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8. 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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9. 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, Juanita, Culmer, Dawn, Daly-Barnes, Kristie, Evensen, Erick, Saavedra, Rubin, Dean, John, Dezube, Milana, Diner, Jaime, Dodis, Regina, Dostou, Jean, Duclos, Michelle, Elmore, Miles, Ferree, Kristin, Foster, Leslie, Fuller, Gail, Garner, Susan, Godwin, Sarah, Goley, April, Gore, Whitney, Green, Brenda, Harris, Elizabeth, Harris, Joy, Harris, Rebecca, Hatharasinghe, Roger, Herring, Charles, Hill, Chernessa, Holmes, Robert, Hutchens, Erin, Jennings, Stuart, Kaake, Ashley, Kaygun, Handan, Kirkman, Marian Sue, Kretzschmar, Heather, Lang, Jaqueline, Largay, Joseph, Lewis, Melissa, Long, Maria Ann, Lucas, Kathryn, McCall, Roshanda, McDaniel, Catrina, McGinnis, Lee Ann, Mogabgab, Edward, Montero, Manuel, Montgomery, Richard, Moran, Joseph, Morgan, Katie, Motley, Taylor, Narendran, Mahendra, Narron, Brooke, Newman, Walter, Nicholson, John, Norris, Stephanie, Norton, Jennifer, Nowell, Erin, O'Brien, Heather, Otero, Heydin, Perkins, Victoria, Quesada, Reyna, Raad, George, Raley, Rosalie, Raman, Sujatha, Rappaport, Jonathan, Ray, Robert, Ray, Shannon, Rice, Lucian, Roberts, Christine, Ross, Kaylee, Scanlon, Erica, Schroder, Derek, Schulte, Michelle, Schultzaberger, Richard, Shoffner, Sylvia, Skrzynski, Michael, Smith, Brian, Smith, Holly, Smith, Jennifer, Smith, Justin, Smith, Kendall, Smith, Leigh, Sparks, Jeffrey, Speece, Jessica, Spivey, Jessica, Stebich, Andrew, Temple, Karen, Tessena, Boryana, Thompson, Casey, Traylor, Henry, Turner, Juliana, Turner, Sh-Rhonda, Van Cleeff, Martin, Vukojicic, Katarina, Wanchick, Leslie, Weinrib, Stephen, Werner, Devorah, Wishon, Candace, Wilson, Jonathan, Wilson, Stephanie, Wright, Heather, Young, Laura, Brown, Jamie, Lillestol, Michael, Allen, Mary Jo, Barker, Bruce, Bedel, Gary, Beuerlein, Shawn, Bhati, Amar, Breslaw, Nicole, Brown, April, Burtch, Brian, Check, Ellen, Chiodi, Shawnie, Colosimo, Linda, Cope, Kathie, Coressel, Denise, Cramer, Bethany, Crowel, Amy, Daboul, Nizar, DeLong, Rebecca, Dirkes, William, Farooki, Zia, Fixler, Don, Friedhof, Linda, Griffen, Julie, Hagan, Anjani, Haney, Kevin, Harris, Kira, Hoffmann, Amanda, Hsieh, Ronald, Ismail-Beigi, Faramarz, Kelso, Kim, Khamousia, Nidaa, Kremer, Gerald, Krol, Adrienne, Kulow, Tanya, Kuttler, Mary, Lee, Andy, Leksan, Jane, McElroy-Marcus, Susan, McNeil, Donald, Mulligan, Guy, Pantalone, Kevin, Perrino, Frank, Peysha, Lori, Pickett, Alicia, Pritchard, James, Provanzana, Kathleen, Rancitelli, Philip, Raupp, Randa, Schnall, Adrian, Siddiqui, Jaweriah, Smith, Cynthia, Sood, Ajay, Sortor, Jennifer, Spinelli, Kristin, Taylor, Diana, Thornton, Aaron, Tiktin, Margaret, Twine, Melissa, Urbank, Ann, Voegele, Francis, Wang, Lawrence, Weiss, Daniel, Werner, Amanda, Williams, Daniel, Wilson, Charles, Aberle, Teresa, Arcon-Rios, Sirlys, Arodak, Bassam, Aziz, Ammara, Bixler, Lacey, Brisko, Carolann, Cannon, Melanie, Choe, James, Connery, Lisa, Elkosseifi, Myriam, George, Aja, Hummer, Kimberly, LaBryer, Lauren, Lane, James, Lim, Jonea, Mirza, Lubna, Mittadodla, Saritha, Priest, Diane, Rao, Veitla, Ricci, Cassie, Salazar, Jennifer, Shaw, Jessica, St John, Jennifer, Talsania, Mitali, Joarder, Farahnaz, Riddle, Matthew, Yuen, Kevin, Ahmed, Intekhab, Austin, Barry, Bagnata, Linda, Bartkowiak, Anthony, Batrus, Jennifer, Baumgarten, Thomas, Belejchak, Paula, Belucher, Christine, Benton, Julia, Berger, Peter, Biscoveanu, Mihaela, Blasick, Abbie, Blyler, Kay, Casey, Linda, Chandler, Bronell, Chapman, Kim, Chou, Brian, Cisar, Jennifer, Clatterbuck, Tabetha, Cook, Richard, Cook II, Richard, Dardi, Inderpreet, DeSalle, Dina, Edevane, Shari, Elliott, Kelsey, Everhart, Brian, Furlong, Kevin J., Geishauser, Jennifer, Goisse, Marcy, Goodman, Yvonne, Gordon, Murray, Gutowski, Catherine, Harris, Ronald, Hu, Ying, Hull, Jenny, Iachini, Kathleen, Iannamorelli, Anthony, Jabbour, Serge, Jackson, Timothy, Jameson, Brian, Janosov, Paula, Jordan, Terry, Kennedy, John, Kurtzer, Gayle, Labuda, Joseph, LaRochelle, Anne, Levinson, Lawrence, Madder, Robert, Marconnet, Kari, Mareda, Patricia, Michael, Donna, Michaels, Debra, Miller, Cathy, Miller, Jeffrey, Minnock, Ann, Mitchell, Michele, Moturi, Hemlata, Moyer, Heather, Nagelberg, Steven, Oliver, Michael, Pepe, Constance, Porter, Patricia, Posey, Dora, Purighalla, Raman, Redmond, Jessica, Reiling, Joseph, Reiling, Susan, Rine, Kathy, Rust, William, Sandutch, Jill, Shaffer, Anette, Shalongo, Annette, Shawley, Sarah, Shonk, Pamela, Singh, Vinay, Slucki, Andrea, Spiller, Kellie, Springer, Nina, Sprouse, Heidi, Sun, Albert, Taylor, Judith, Watine, Robert, Watkinson, Jean, Weaver, Nancy, Wenocur, Howard, Yeoman, Gary, Ackermann, Jeremy, Averill, Nathan, Ballard, Thomas, Byars, William, Carter, Caroline, Castay, Cathleen, Cheek, Shonda, Collins, Jessica, Collins-Jamison, Traci, Cooksey, Erin, Crockford, Nicole, Cutshall, Christopher, Dar, Moahad, Drake, Almond, Dugat, Kameron, Durham, John, Durham, Nancy, Eagerton, Donald, Edmonds, Nataish, Farmer III, Joseph, Fogarty, Charles, Gatlin, June, Geisberg, Harry, Grossman, Margaret, Harrell, Wendy, Harrison, John, Harrison, Kristina, Heincelman, Sarah, Holladay, Lauren, Huberty, Chad, Isakov, Ingrid, Jordan, Norma, Kunkel, Michael, Laserna, Susan, Lawrence, Amanda, Lawrence, Andrew, Livingston, Yolanda, Lloyd, Eric, Lopez, Lina, Manuel, Joyce, Mayfield, Ronald, McDonald, Margaret, Morgan, Caroleann, Munn, Joanie, Murphy, Lauren, Nicol, Brent, Nicol, Philip, Norris, Rebecca, Phillips, Bunny, Reeves, Angela, Roach, Jacqueline, Ross, Irene, Santi, Jeffrey, Saunders, Jacqueline, Shugart, Henry, Singleton, Monnieque, Slee, Erin, Smalley, Kathleen, Smith, Kristy, Sofley, Carl, Solheim, Vesna, Spell, Samantha, Tanenberg, Robert, Whitley, Chester, Widel, Michele, Wilhoit, Gordon, Wood, Ruth, Wright, Jaime, Wulf, Alissa, Zapkowski, Julie, Adams, Kristi, Adams, Roberta, Ananthula, Parvati, Bass, Caitlin, Bates, Chad, Baum, Howard, Bays, Anna, Beck, Teresa, Bilbrey, Brett, Brown, Ashley, Carlton, Anna, Carter, Jenny, Cheri, Laura, Childress, Richard, 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, Annamalai, Rajasekaran, Arain, Khadija, Arellano, Angelica, Arispe, Barbara, Aronoff, Stephen, Arroyo, Jesus, Bachand, Trista, Bailey, Becky, Bajaj, Chris, Banarer, Salomon, Barnella, Christine, Bartz, Mary, Bates, Jason, Becerra, Karen, Benavides, Melissa, Bhuchar, Subodh, Blevins, Thomas, Bonazzi, Amanda, Brinson, Cynthia, Brown, Timiki, Buckley, Brandee, Bunker, Christy, Burbano, Jose, Busch, Vickey, Bustamante, Rosibel, Calais, Natalee, Camacho, Allison, Camp, Shana, Canada, Nancy, Canchola, Daniel, Cano, Monica, Cardenas, Veronica, Carl, Leighton, Casaubon, Luis, Castaneda, Jessica, Castro, Cindy, Ceniceros, Diego, Chaicha-Brom, Tira, Chaudhuri, Sudipta, Chavez-Velazquez, Alberto, Chen, Jocelyn, Cheyne, Theresa, Chilka, Sapna, Chionh, Kristen, Chunawala, Imran, Cope, Pamela, Cotton, Sonja, Daudjee, Munib, Davidson, Tichina, De Loa, Geraldine, Deniega, Ann, Dillow, Naco, Dominguez, Michael, Dorfman, Steven, Doshi, Ankur, Dunnam, Theresa, Dutta, Papiya, Eiler-Prater, Megann, 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, Randall, Scribner, Anita, Shah, Arunkumar, Shaw, Stephanie, Shirley, Jefferey, Shook, Mindy, Siddiqui, Muhammad, Sims, Jamie, Singh, Kamalpreet, Skero, Jennifer, Smejdir, Debra, Stacey, Amy, Strzinek, Robert, Tan, Anjanette, Tayabali, Khadija, Tercero, Almundena, Terry, Jessica, Tinney, Irene, Toe, Florence, Toler, Sara, Tripathy, Devjit, Tumyan, Anna, Ulrich, Michelle, Underwood, Krissandra, Valdez, Christina, Valdivieso, April, Vanderheiden, Anna, Vandre, Morgan, Vardeman, Megan, Vargas, Richard, Vilchis, Monica, Warne, Desiree, Wallace, Jeannine, Weindorff, Kathleen, Welch, Heather, Wellmon, Brandy, Werntz, Gary, White, Leta, Williams, Tearani, Wilson, Maria, Wilson, Robyn, Wilson, Ronald, Wood, John, Wright, David, Yeatts, Rhonda, Zahir, Rezwana, Crockett, Becky, Fawson, Ashlee, Graham, Timothy, Mitchell, Zachary, Quinn, Sally, Reddy, Deepika, Rhudy, Jackson, Rosen, Priscilla, Shakespear, Kaylynn, Simmons, Debra, Turner, Ashley, Vanderhoof, Erin, Wahl, Matthew, Zubair, Imran, 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

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