BACKGROUND: Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients. 

PATIENTS AND METHODS: Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks.

African Americans constituted 36% of enrolled patients. 

• Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. 
• Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation.

 RESULTS: For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo).

 CONCLUSIONS: In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.

Similarly, Finer, Bloom and colleagues studied weight loss in people with type 2 diabetes who were treated with sibutramine.

• AIM: To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. 

• METHODS: Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. 

Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. 

Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements.

 Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals.

 RESULTS: Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine.

 Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat).                                                                                                                                                The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30).                                      Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001).                                                                                                                                            Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG.

•  CONCLUSIONS: Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment

• Same conclusion for Fujioka K; Seaton TB; Rowe E; Jelinek CA; Raskin P; Lebovitz HE; Weinstein SP  of the
  Nutrition and Metabolic Research Center, Scripps Clinic, San Diego, CA 92130, USA,[50]

• Efficacité et sécurité de la sibutramine chez les obèses, dont le diabétiques de type 2 est mal contrôlé par le régime et un médicament anti diabétique.

  To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent.

•  

  AIM: To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent. METHODS: This study was a 24-week, double-blind, multicentre trial following a 5-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) > or =27 kg/m2) patients with poorly controlled type 2 diabetes mellitus were randomized either to sibutramine (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; mean age 55 years; mean weight 98.2 kg) at 16 participating centres. To achieve moderate calorie restriction (deficit > or = 250-500 kcal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly through week 6, and maintained at 20 mg through week 24). The main outcome measures included changes in weight, b.m.i., waist and hip circumference, glycaemic control, lipid profile, and quality of life, and evaluation of reported adverse events. 

  RESULTS: Sixty-seven per cent of sibutramine patients and 71% of placebo patients completed the study. At week 24 when comparing those who completed the course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. -0.5%) weight loss. Weight loss > or =5% or 10% was achieved by 33% and 8% of sibutramine patients, respectively, but no placebo patients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean treatment differences were -0.53% and -1.65% (p < or = 0.05), respectively, for HbA1c, and -1.4 mmol/l (p < or =0.05) and -3.8 (p < or =0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycerides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramine was well tolerated compared with the placebo. Sibutramine treatment was associated with small mean increases in blood pressure (BP) and pulse, although an increase in BP was not seen in sibutramine-treated patients who lost > or = 5% of their weight.

   CONCLUSIONS: Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate caloric restriction. This weight loss was associated with improvements in metabolic control and quality of life, and sibutramine was generally well tolerated in obese patients with type 2 diabetes

   

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