OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin and noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double-blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-week period. Advice on diet and behaviour modi®cation was provided. One follow-up was conducted four weeks after cessation of treatment. SUBJECTS: 235 obese outpatients, aged 18±65 y with a body mass index (BMI) within the range 27±40 kgam 2 . MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, satiety, appetite and craving for sweet, savoury and carbohydrate foods, and also for carbohydrate snacking, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: The group mean ( AE s.e.m.) weight loss at end-point was 1.4 AE 0.5 kg for placebo (n 59), 2.4 AE 0.5 kg for 5 mg sibutramine (n 56), 5.1 AE 0.5 kg for 10 mg sibutramine (n 59) and 4.9 AE 0.5 kg (n 62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg groups was statistically signi®cant from week 2 onwards (P`0.01), but there was no signi®cant difference between these sibutramine groups. The percentage of patients losing b 5% of initial bodyweight was signi®cantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49%) than for treatment with placebo (19%), (P`0.001). During the double-blind period, 41 patients (17%) withdrew prematurely and 168 patients (71%) reported 453 adverse events. The incidence and type of adverse event and the rates of withdrawal, were not signi®cantly different in the four groups. No signi®cant differences between the groups were observed, in respect of changes in systolic and diastolic blood pressure, but a signi®cant increase in heart rate (about 4 beatsamin) was noted for patients who received 10 mg or 15 mg sibutramine, compared with the placebo (P`0.001).CONCLUSION: These data demonstrate dose-related weight loss with sibutramine treatment for up to 12 weeks in obese patients. Doses of 10 mg and 15 mg once daily were shown to be similarly effective, well tolerated and signi®cantly more effective than the placebo.

Most patients with hypertension need more than one drug to achieve blood pressure (BP) control. This randomized, double-blind, multifactorial study evaluated whether combinations of aliskiren and amlodipine provided superior BP reductions to component monotherapies in patients with hypertension (mean sitting diastolic BP (msDBP) 95-<110 mm Hg). Overall, 1688 patients were randomized to once-daily monotherapy with aliskiren 150 or 300 mg or amlodipine 5 or 10 mg, combination therapy with one of four corresponding aliskiren/amlodipine doses, or placebo for 8 weeks. At week 8 end point, aliskiren/amlodipine combinations provided significant msDBP reductions from baseline of 14.0-16.5 mm Hg, compared with reductions of 8.0 and 10.2 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 11.0 and 13.8 mm Hg for amlodipine 5 and 10 mg, respectively (P<0.05). Aliskiren/amlodipine combinations provided reductions in mean sitting systolic BP 20.6-23.9 mm Hg, compared with decreases of 10.7 and 15.4 mm Hg for aliskiren 150 and 300 mg, respectively (P<0.001), and 15.8 and 21.0 mm Hg for amlodipine 5 (P< or =0.001) and 10 mg (P=NS), respectively. Aliskiren/amlodipine combination therapy provides greater BP lowering than either agent alone, hence offering an effective treatment option for patients with hypertension.