Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. Effects of orlistat on obesity-related diseases - a six-month randomized trial.
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.
                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.
                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).
                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. Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control. To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives.
                Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed.
                Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04).
                A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction. This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4+/-9.6 to 70.0+/-9.5 kg in the sibutramine group and from 77.9+/-9.0 to 74.5+/-9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8+/-5.8 mm Hg after stabilization and 125.2+/-8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4+/-3.7 and 81.5+/-4.6 mm Hg. With placebo, blood pressure dropped from 129.0+/-7.1/80.9+/-4.9 mm Hg to 122.8+/-9.7/80.3+/-5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary. To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months.
                The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo.
                The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change.
                The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy. To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index (BMI) of > 28 kg/m2 and poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia.
                This trial was a six-month, randomized, double-blind, placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet. 1004 obese patients (BMI 28-40 kg/m2) were included by 253 private endocrinologists and received orlistat (n = 499) or placebo (n = 505). Patients were stratified by concomitant disorder (type 2 diabetes, n = 193; hypertension, n = 614; hypercholesterolaemia, n = 197). Body weight, anthropometry, lipid and glycaemic control parameters and blood pressure.
                After six months, orlistat produced a significantly greater weight loss than placebo in type 2 diabetes (-4.2% vs. -1.4%), hypertension (-6.2% vs. -1.9%) and hypercholesterolaemia (-5.5% vs. -2.3%) groups (p < 0.0001 for all). There was a greater decrease in HbA(1c) in the type 2 diabetes group (-0.54 vs. -0.18%; p = 0.002) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group (-11.7% vs. -4.5%; p = 0.004) with orlistat vs. placebo. Early weight loss (> or = 5% at 12 weeks) was associated with the highest weight loss in each group, and the highest decreases in HbA1c, LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes, hypercholesterolaemia and hypertension, respectively, at six months. The incidence of adverse events was similar for orlistat and placebo, except for certain generally well-tolerated gastrointestinal events that were more common with orlistat.
                Orlistat plus a mildly reduced-calorie diet produced clinically meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia.
                Copyright 2004 Blackwell Publishing Ltd
In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being.