The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period

Abstract

Background: Obesity, type 2 diabetes mellitus (T2D) and unhealthy blood lipid profile are strongly associated with the risk of developing cardiovascular disease (CVD). We examined whether blood lipid changes with short term administration of the weight lowering drug, sibutramine and lifestyle modification in obese and overweight high-risk patients was associated with T2D status at screening.

Methods: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial included obese and overweight patients at increased risk of cardiovascular events. All patients received guidance on diet and exercise plus once-daily 10 mg sibutramine during the 6-week, single blind lead-in period. Multivariable regression models were used to investigate factors associated with changes in lipid levels during the first four weeks of treatment.

Results: A total of 10 742 patients received at least one dose of sibutramine during the 6-week lead-in period of SCOUT. After four weeks, patients experienced mean reductions in low density lipoprotein (LDL-C) 0.19 mmol/L, high density lipoprotein (HDL-C) 0.019 mmol/L, very low density lipoprotein (VLDL-C) 0.08 mmol/L, total cholesterol (TC) 0.31 mmol/L and triglycerides 0.24 mmol/L (p < 0.0001 for each). Four week changes in LDL-C, HDL-C and total cholesterol for patients without vs. with T2D were: LDL-C:-0.25 mmol/L vs. -0.18 mmol/L, P = 0.0004; HDL-C: -0.03 mmol/L vs. -0.02 mmol/L, P = 0.0014; total cholesterol: -0.37 mmol/l vs. -0.29 mmol/l, P = 0.0009. Multivariable regression analysis showed that similar decreases in body mass index (BMI) affected lipid changes differently according to diabetes status. A 1 kg/m2 decrease in BMI in patients with T2D was associated with -0.09 mmol/L in LDL-C (P < 0.0001) and -0.01 mmol/L in HDL-C (P = 0.0001) but larger changes of -0.16 mmol/L LDL-C and -0.03 mmol/L in HDL-C (P < 0.0001 for both) in patients without T2D.

Conclusion: Short term weight management with sibutramine therapy in obese or overweight high-risk patients induced significant mean reductions for all lipids. Those without T2D benefited most. Patients with hyperlipidaemia and the less obese patients also had greater falls in LDL-C and TC during weight loss. The trial is registered at ClinicalTrial.gov number: NCT00234832.

Figures

Figure 1

Mean lipid changes in patients with T2D according to BMI reduction quartiles. Lipid changes in patients with T2D stratified according to BMI reduction quartile (1-4). Quartile 1 represents the least reduction in BMI whereas quartile 4 represents the greatest. Mean lipid values are listed for each quartile with 95% confidence intervals. All values are measured in mmol/L. 13 patients with unknown risk category were excluded.

Figure 2

Mean lipid changes in patients without T2D according to BMI reduction quartiles. Lipid changes in patients without T2D stratified according to BMI reduction quartile (1-4). Quartile 1 represents the least reduction in BMI whereas quartile 4 represents the greatest. Mean lipid values are listed with 95% confidence intervals. All values are measured in mmol/L. 13 patients with unknown risk category were excluded.

Figure 3

The effects of T2D and 1 kg/m2 BMI-decrement in patients with/without T2D on predicted lipid changes. Multivariable regression analysis demonstrating the effects of a 1 kg/m2 BMI decrement in patients with/without T2D and the effect of T2D on predicted lipid changes. The model is adjusted for all covariates in Table 1. 13 patients with unknown risk category were excluded.