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ABSTRACT: The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular disease.
HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using Cox regression models.
Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA(1c) available at baseline (i.e. study randomisation). Median age was 62 years (range 51-86 years), median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were women. The median HbA(1c) concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150 mmol/l]) and median diabetes duration was 7 years (0-57 years). For each 1 percentage point HbA(1c) increase, the adjusted HR for the primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12 for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA(1c) increase (p = 0.02 for interaction). There was no evidence of increased risk associated with HbA(1c) ≤ 6.4% (≤ 46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of cardiovascular disease did not modify the associations.
In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA(1c) concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-cause mortality.
Diabetologia 05/2012; 55(9):2348-55. · 6.81 Impact Factor
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L F Van Gaal, I D Caterson,
W Coutinho,
N Finer,
A P Maggioni,
A M Sharma,
C Torp-Pedersen,
H Ge,
S A Moran,
G M Shepherd,
W P T James
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ABSTRACT: To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.
SCOUT is an ongoing, prospective, randomized, double-blind, placebo-controlled outcome trial in cardiovascular high-risk overweight/obese patients. A total of 10 742 patients received single-blind sibutramine and individualized weight management during the 6-week lead-in period; 84% had a history of type 2 diabetes mellitus and additional co-morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses between patients with and without diabetes.
Concomitant antidiabetic medication use was reported by 86% of the diabetic patients (approximately 30% required insulin-alone or in combination). Body weight and waist circumference decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm (both men and women); blood pressure (BP) was also reduced (median systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who were hypertensive and/or lost the most weight (>5%). In diabetic patients who entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245), increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg). Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0 bpm).
In these high-risk diabetic patients, sibutramine and lifestyle modifications for 6 weeks resulted in small, but clinically relevant, median reductions in body weight, waist circumference and BP. A small median increase in pulse rate was recorded.
Diabetes Obesity and Metabolism 09/2009; 12(1):26-34. · 3.38 Impact Factor
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ABSTRACT: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial.
SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed.
At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by median [5th, 95th percentile] of -6.5 systolic [-27.0, 8.0] and -2.0 diastolic [-15.0, 8.0] (p < 0.001). Hypertensive patients with no weight loss or with weight gain had median decreases of -3.5 systolic [-26.0, 10.0] and -1.5 diastolic [-16.0, 9.0] (p < 0.001). Normotensive patients had median increases of 1.5 systolic [-15.0, 19.5] and 1.0 diastolic [-10.5, 13.0] (p < 0.001) attenuated with increasing weight loss. Approximately 43% of patients initially categorized as hypertensive had a lower blood pressure category at end-point. Concomitant antihypertensive medication classes did not affect blood pressure reductions. Pulse rates were uniformly elevated (median 1-4 bpm, p < 0.001) across blood pressure and weight change categories.
In hypertensive patients (>or=140/>or=90), blood pressure decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal blood pressure (<130/<85), weight loss of >5% induced decreases in systolic blood pressure; otherwise, small increases were observed. Small pulse rate increases were observed regardless of blood pressure or weight change status.
Diabetes Obesity and Metabolism 07/2008; 11(3):239-50. · 3.38 Impact Factor
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W. P. T. James, I. D. Caterson,
W. Coutinho,
N. Finer,
L. F. Van Gaal,
A. P. Maggioni,
C. Torp-Pedersen,
A. M. Sharma,
G. M. Shepherd,
R. A. Rode,
C. L. Renz,
Scout Investigators
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ABSTRACT: BACKGROUND The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P = 0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P = 0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P = 0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause.
New England Journal of Medicine. 363(10):905-917.
