SCOUT Trial Results Reveal Meridia Health Risks

SCOUT trial results indicate obesity drug treatment sibutramine ( Meridia/Reductil) increases health risks in obese or overweight patients with cardiovascular risk factors

The Sibutramine Cardiovascular OUTcomes (SCOUT) trial is a long-term study undertaken by Abbott in order to determine the safety of sibutramine in patients with a history of cardiovascular disease. However, outcomes for this trial have shown that rather than improving cardiovascular risk in this group of patients, sibutramine increases the risk for cardiovascular events.

Abbott’s Sibutramine (Reductil/ Meridia), an Obesity Drug Treatment

Abbott’s sibutramine is an appetite suppressant that has been available in the European Union since 1999 and in the USA since 1997. The weight loss drug is indicated for the weight management in conjunction with a reduced calorie diet in obese patients and in overweight patients who also have other obesity related diseases, such as type-2 diabetes or dyslipidaemia. The obesity drug treatment is still available in the USA under the brand name of Meridia, and is known in Europe under brand names including Reductil, Ectiva, Sibutral, Reduxade and Zelium.

What is the Sibutramine Cardiovascular OUTcomes (SCOUT) Trial?
The SCOUT trial is a large phase III US-based trial that began in 2002 and enrolled nearly 10,000 patients. It investigated long-term use of sibutramine compared to placebo in patients who were obese or overweight and presented with known or high risk of cardiovascular disease.

The inclusion criteria for the study were that SCOUT study participants:

  * be 55 years of age or older,
  * have a Body Mass Index (BMI) between 27- 45 kg/m2 or a BMI is between 25- 27kg/m2 with a waist circumference greater than 102 cm for males and 88 cm for females; and
  * are at high cardiovascular risk.

High cardiovascular risk for the SCOUT trial is defined as belonging to one of the following:

  * Type 2 diabetes with another cardiovascular risk factor, such as controlled hypertension, dyslipidaemia, a smoker, or diabetic nephropathy;
  * a medical history positive for a cardiovascular event e.g. myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary Angioplasty , or coronary artery disease; or
  * Type 2 Diabetes alongside another risk factor and a medical history of a previous cardiovascular event.

Note: A person is overweight when their BMI lies between 25 and 30kg/m2, while an obese person has a BMI of 30kg/m2 or greater.
Aim of the SCOUT Study

The SCOUT study aimed to investigate the impact of long-term sibutramine treatment on cardiovascular endpoints in the selected group of patients in the hope that the weight loss drug would improve such outcomes.

The primary endpoint for the study was the length of time to the first occurrence of any cardiovascular event including a combination of heart attack, stroke, resuscitated cardiac arrest or death.

The secondary endpoint for the SCOUT study included All-Cause Mortality, which is the number of deaths during the trial, regardless of the cause of death.

In order to evaluate the effect of sibutramine treatment on these endpoints, Abbott compared the number of events between the following two groups of patients:

  * patients who were received sibutramine treatment in conjunction with diet and counselling
  * patients who received placebo in conjunction with diet and counselling

SCOUT Study Results for Sibutramine in Obese Or Overweight Patients with Cardiovascular Risk

According to the FDA, preliminary findings from the SCOUT trial have indicated that long-term sibutramine treatment is associated with an increased cardiovascular risk.

In the FDA’s Early Communication regarding the ongoing safety review for sibutramine, the agency states:

“The preliminary data shows that cardiovascular events were reported in 11.4% of patients using sibutramine compared to 10% of patients using a placebo. This difference is higher than expected, suggesting that sibutramine is associated with an increased cardiovascular risk in the study population.”

Although this difference may seem small, considering around 5000 patients would have been assigned to each arm, this represents an estimated extra 70 patients who experienced a cardiovascular event in the sibutramine arm compared to the placebo arm. This clearly represents a concern for regulators, who have recently reviewed the status of sibutramine as an approved obesity treatment.

Sources:

Clinicaltrials.gov 2009, ‘A Long Term Study of Sibutramine and the Role of Obesity Management in Relation to Cardiovascular Disease in Overweight and Obese Patients (SCOUT)’, Last updated April 17 2009

FDA 2009, ‘Early Communication about an Ongoing Safety Review of Meridia (sibutramine hydrochloride)’, 20 November 2010

Christine Redmond