A Review of the Metabolic Effects of Sibutramine

T. D. Filippatos; D. N. Kiortsis; E. N. Liberopoulos; D. P. Mikhailidis; M. S. Elisaf

Disclosures

Curr Med Res Opin. 2005;21(3):457-468. 

In This Article

Effects on Lipids

Gokcel et al .[50] evaluated the efficacy of sibutramine (10 mg twice a day) on 50 obese women. At the end of the 24-week study, total cholesterol (-12.88%), low density lipoprotein (LDL) cholesterol (-18.52%), triglycerides (TG) (-15.84%) and apolipoprotein B (apoB) (-13.27%) were significantly decreased (all p < 0.01 vs. baseline). In this study,[50] sibutramine compared to orlistat administration ( n = 50 in each group) resulted in a more pronounced decrease in the levels of fasting blood glucose (15.95% vs. 10.95%), fasting insulin (29.07% vs. 22.84%), HOMA index (38.63% vs. 32.73%), total cholesterol (12.88% vs. 7.99%), LDL cholesterol (18.52% vs. 9.18%) and uric acid (11.98% vs. 8.61%) together with a rise in HDL cholesterol (1.21% vs. 1.03%). On the other hand, orlistat compared to sibutramine use induced a more marked decrease in serum triglycerides (17.37% vs. 15.84%), systolic BP (4.30% vs. 3.90%) and pulse rate (2.12% vs. 1.64%) despite the differences in weight reduction (sibutramine 13.60% vs. orlistat 9.15%).

Sabuncu et al .[66] reported that sibutramine for 12 months in 72 obese patients resulted in a significant decrease in TG levels and an increase in HDL cholesterol levels (both p < 0.01), but serum total and LDL cholesterol levels did not change significantly. The SAT study[67] recruited 389 obese patients without type 2 diabetes or cardiovascular disease. At the end of this 54 week study, weight loss with sibutramine was accom panied by an improvement in the lipid profile. Compared to baseline, patients receiving sibutramine had a significant increase in mean HDL cholesterol of 0.14 mmol/L (5.6 mg/dL) versus an increase of 0.10 mmol/L (3.9 mg/dL) in the placebo group (both p < 0.001).

Weight loss has a favourable effect on serum lipoprotein( a) [Lp(a)] levels.[68,69] Interestingly, Muls et al .[70] and Kiortsis et al .[71] reported that a short-term weight loss in obese patients resulted in a decrease of Lp(a) levels only in individuals with pre-treatment Lp(a) above 30 mg/dL and 20 mg/dL, respectively. In one study[50] sibutramine treatment resulted in a significant reduction of Lp(a) levels (-7.8%, p < 0.01 vs. baseline).

In the study of Dujovne et al .[72] , 322 dyslipidaemic obese patients (BMI ≥27 kg/m2) with serum TG levels ≥2.8 mmol/L (250 mg/dL) and ≤11.3 mmol/L (1000 mg/ dL) and serum HDL cholesterol levels ≤1.16 mmol/L (45 mg/dL) (women) and ≤1.04 mmol/L (40 mg/dL) (men) were randomised to sibutramine 20 mg once daily or placebo for 24 weeks. At the end of this study the patients taking sibutramine had significantly greater mean weight loss than those receiving placebo (-4.9 kg vs. -0.6 kg, p < 0.05). Forty-two per cent in the sibutramine group lost ≥5% of baseline weight and 12% lost ≥10% compared with 8% and 3%, respectively, in the placebo group ( p < 0.05). Mean decreases in serum TG levels among 5% and 10% weight-loss responders in the sibutramine group were 0.37 mmol/L (33.4 mg/ dL) and 0.81 mmol/L (72.3 mg/dL), respectively, compared with an increase of 0.36 mmol/L (31.7 mg/ dL) among all patients receiving placebo ( p < 0.05). Mean increases in serum HDL cholesterol levels for 5% and 10% weight-loss responders in the sibutramine group were 0.12 mmol/L (4.9 mg/dL) and 0.17 mmol/L (6.7 mg/dL), respectively, compared with an increase of 0.04 mmol/L (1.7 mg/dL) among all patients in the placebo group ( p < 0.05). Correlations between weight loss and observed serum TG and HDL cholesterol changes were demonstrated for sibutramine-treated and placebo-treated patients ( p < 0.05), indicating that, in general, improvement in serum lipids is proportional to the degree of weight loss. In the STORM study[23] after 2 years of sibutramine treatment there was a 20.7% increase in HDL cholesterol levels in the sibutramine group, while in the placebo group there was only an 11.7% increase ( p < 0.01). Further more, in this study the reductions of very low density lipoprotein (VLDL) cholesterol and TG observed over the first 6 months were sustained in the sibutramine group, but not in the placebo group. Importantly, changes in the concentrations of HDL cholesterol, VLDL cholesterol and TG, but not LDL cholesterol, exceeded those expected from weight loss alone. A similar increase in HDL chol esterol levels after sibutramine treatment for 12 months, following a 4-week very low caloric diet, has been reported ( p < 0.01 vs. placebo).[73]

McMahon et al .[22] assessed the capacity of sibutramine to promote and maintain weight loss in obese patients with controlled hypertension. At the end of this 52-week study, 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 receiving placebo ( p < 0.05). There was a significant reduction of TG in the 5% and 10% responders in the sibutramine group ( p < 0.05 vs. all patients receiving placebo). More over, there was a significant increase in HDL cholesterol levels in all patients receiving sibutramine (both p < 0.05 vs. all patients receiving placebo).

Another group[58] studied the effects of sibutramine treatment in obese diabetic patients. After treatment for 6 months, there was a significant reduction in total cholesterol (-12.5%), LDL cholesterol (-18.2%), VLDL cholesterol (-13.5%), TG (-16%), apoB (-13.5%) and Lp(a) (-7.7%) (all p < 0.05 vs. baseline), while in the placebo group only LDL cholesterol decreased significantly (by 9.7 %). Moreover, in a 12-month study[74] weight loss with sibutramine was associated with a significant increase in HDL cholesterol (+4.4% vs. - 3.4% in the placebo group, p < 0.01 between treatment groups) and a significant reduction in TG (-17.5% vs. - 7.9% in the placebo group, p < 0.01 between treatment groups).

Sibutramine reduced total and LDL cholesterol in most trials, but this reduction was not significantly different compared to placebo. Moreover, sibutramine helped to maintain the decreases in total and LDL cholesterol observed after weight loss, but again this effect did not reach statistical significance compared to placebo. On the other hand, sibutramine in most trials reduced the total:HDL cholesterol ratio, a predictor of risk of vascular events. A study group[73] reported a significant reduction (-0.6) of this ratio in the sibutramine group after 12 months of treatment following a very low calorie diet. Furthermore, at the end of the STORM study there was a significant reduction (-0.7) of this ratio in the sibutramine group ( p < 0.01 vs. placebo group).[23]

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