Sibutramine is a
serotonin-
noradrenaline reuptake inhibitor that is effective for long-term
weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of
noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of
sibutramine for
weight loss in obese patients whose
hypertension was well controlled (DBP < or = 95 mm Hg) by
beta-adrenergic blocking agents (beta-blockers), with or without concomitant
thiazide diuretics. Of the 61 patients randomised to
sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks,
sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean
weight reductions were 4.2 kg (4.5%) in the
sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater
weight reduction on
sibutramine was accompanied by trends for greater mean reductions in serum
triglycerides and
very low density lipoprotein cholesterol.
Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No
sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the
sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the
sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the
sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in
sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary,
sibutramine was well tolerated and effective in
weight reduction. The addition of
sibutramine did not result in an increase in BP in obese patients whose
hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with
sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.