Effect of Sibutramine on Cardiovascular Outcomes in Overweight and Obese Subjects

Abstract

Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P = 0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.

Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes

“…showed a significantly higher risk of a primary CV outcome event in the sibutramine group than in the placebo group 59 . However, greater weight loss was associated with reduced overall CV risk in both groups 60 .Sibutramine was withdrawn from the market due to an uncertain benefit-risk balance, even in patients with T2DM.…”

Cardiac arrest caused by sibutramine obtained over the Internet: a case of a young woman without pre‐existing cardiovascular disease successfully resuscitated using extracorporeal membrane oxygenation

“…This mechanism may cause prolongation of the QT interval. Unfortunately, the effect of sibutramine on the QT interval was not evaluated in the SCOUT study 3. Nevertheless, the findings in the cases of cardiac arrest associated with sibutramine suggest that this agent should be avoided in patients already taking medications that potentially prolong the QT interval.…”

“…The Sibutramine Cardiovascular and Diabetes Outcome Study (SCOUT) showed that treatment with sibtramine for 5 years in subjects with pre‐existing cardiovascular diseases significantly increased non‐fatal myocardial infarction and non‐fatal stroke, although the number of cardiovascular deaths or all‐cause mortality was not increased 3. Because the benefits of sibutramine do not outweigh the risk of the cardiovascular events, it has been withdrawn by the USA and European Union.…”

Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

“…17 After physicians prescribed the drug for longer than a decade, the 2010 Sibutramine Cardiovascular Outcomes Trial (SCOUT), a randomized cardiovascular outcomes study in patients with cardiovascular disease, diabetes mellitus (DM), or both, found that sibutramine caused a greater rate of cardiovascular events. 18 In post hoc analysis by an FDA regulator, changes in BP did not predict these events, leaving the possibility of an unidentified mechanism of harm. 19 Some felt this signal for harm in high-risk patients should not be generalized to lowerrisk patients, who might lose weight without an increase in cardiovascular risk.…”

“…19 Some felt this signal for harm in high-risk patients should not be generalized to lowerrisk patients, who might lose weight without an increase in cardiovascular risk. 18 Others felt that patients with subclinical cardiovascular disease would be difficult to identify. 15 Ultimately, sibutramine was voluntarily removed from the market in 2010.…”