There were statistically significant changes in triglycerides compared with placebo (+3.2%) at month 6 for the sibutramine 10- and 15-mg treatment groups (-10.8%, P <.05 and -10.0%, P <.01, respectively). Uric acid levels were also significantly reduced at month 6 for both sibutramine treatment groups (10 mg, -6.0% [P <.05] and 15 mg, -6.2% [P <.05] compared with placebo, -1.9%). Decrease in uric acid was the only laboratory-reported variable that was statistically significantly greater in the sibutramine-treated patients than in the placebo-treated patients at end point Table 3. These changes are more closely associated with disease end points than with patient outcomes.
Among adverse events occurring with a frequency of more than 5% in any treatment group, only dry mouth occurred significantly more frequently with 10 mg sibutramine (19 patients) or 15 mg sibutramine (21 patients) than with placebo (2 patients; P <.001). Eight serious adverse events led to early withdrawal during the double-blind phase of the study (2 in each of the sibutramine groups and 4 in the placebo group). Two were considered possibly related to sibutramine. The first was a 49-year-old woman with a history of epilepsy with no seizures during the previous 4 years, who was withdrawn after 126 days of treatment with 10 mg sibutramine because she had had 4 “drop attacks” within 2 weeks. The second was a 32-year-old woman who was withdrawn after 246 days of treatment with 15 mg sibutramine because of palpitations due to frequent ventricular ectopic beats. No evidence was found of any withdrawal effect during the follow-up period, when active treatment was over. Patient psychological status was evaluated both at the end of the double-blind treatment (63 patients completed all assessments) and at follow-up 1 week after stopping treatment (67 patients completed all assessments). There were no statistically or clinically significant differences between the treatment groups for change in either the Beck Depression Inventory or the State Anxiety Inventory studied from the end of the double-blind treatment period to the follow-up. All 3 groups showed a mean improvement in the depression inventory.
Mean changes in vital signs averaged over all post-baseline double-blind assessments adjusted for center and treatment-by-center are shown in Table 3. Differences in mean changes in blood pressure were not statistically significant for the sibutramine treatment groups from placebo, except for the mean increase in diastolic blood pressure in the sibutramine 10 mg treatment group Table 3. Statistically significant changes in pulse rate in the sibutramine 15 mg treatment group compared with the placebo treatment group were consistent with the mechanism of action of sibutramine as an SNRI.
Discussion
Weight loss, obesity, and overweight are important topics,16 and today an increasing proportion of obesity is first encountered in the family practice setting.38 Our study shows that in the context of a family practice setting, a patient’s diet, along with sibutramine treatment, will cause more loss of weight than changes in diet alone. Increased levels of total serum cholesterol are associated with an increased risk of coronary heart disease, and although difficult to quantify, a reduction of 0.6 mmol per L has been observed to be associated with a 54% lower risk.39 This was calculated in a retrospective analysis of results of several clinical studies. Patients in this study losing 10% of their body weight over 6 months taking sibutramine 10 mg once daily reduced serum cholesterol by 0.23 mmol per L and may contribute to an overall benefit for patients as part of a risk reduction program. Similarly, the recently recommended target for reduction of triglycerides is a reduction of 1.7 mmol per L.40 In our study, a reduction of 0.63 mmol per L in triglycerides was accomplished among those patients who received sibutramine 10 mg who lost at least 10% of body weight. Mean changes in blood pressure observed during the 6 months of our study were not great enough to increase the category of patient risk for coronary heart disease.41 Although weight loss can be associated with decreased mortality,13 the extent to which a weight reduction of 10% can augment other medical approaches to risk reduction long-term is only now being defined.
In this 1-year placebo-controlled study carried out in the primary care setting, sibutramine given with dietary advice was significantly superior in all weight loss efficacy assessments to dietary advice alone (placebo). These efficacy assessments included the ranked weight reduction outcomes analysis. Sibutramine was consistently superior to placebo across all categories of weight loss in this ranked analysis that takes subject withdrawals into account. The results of this study confirm the findings previously reported.30