SERENADE (Study Evaluating Rimonabant Efficacy in Drug Naive Diabetic Patients) was a six-month phase IIIb, multinational, multicenter, randomized, double-blind and placebo-controlled trial carried out at 56 centers in the United States, Germany, Argentina, Chile, Hungary, Poland and the Netherlands.

The 278 participants enrolled in the trial had Type 2 diabetes for at least two months but less than three years, had an HbA1c level of more than 7 percent but less than 10 percent, and had not been treated with another diabetes drug within six months of the start of the trial.

Patients were randomized to receive for six months either a daily dose of 20 mg of Acomplia, or a placebo along with diet based on the American Diabetes Association recommendations. Those who were overweight also had a 600 calorie reduction in their diet.

The trial showed that HbA1c levels in patients with a baseline average of 7.9 who took a 20 mg Acomplia pill once daily fell 0.8 percentage points compared to a drop of 0.3 points in those taking a placebo.

Patients with an HbA1c level of at least 8.5 when they started taking Acomplia saw their their blood sugar level decrease 1.9 points compared to 0.7 points in patients on a placebo.

Over 50 percent of the patients in the Acomplia arm of the trial achieved HbA1c levels of below 7 percent, the target level for good glucose control recommended by the American Diabetes Association.

The patients taking Acomplia in the trial lost on average 14.8 pounds of weight compared to 5.95 pounds for those on a placebo. The waist circumference of patients on Acomplia shrank an average of 2.34 inches compared to .93 inch for those on a placebo.

Patients in the Acomplia arm of the trial also saw improvements in multiple cardiometabolic risk factors.

HDL (good) cholesterol increased by 10.1 percent compared to 3.2 percent for those on the placebo. Triglyceride levels (bad fat in the blood) decreased by 16.3 percent for those on Acomplia compared to 4.4 percent for those on the placebo.

Fasting plasma glucose decreased by a greater amount in the Acomplia group, and adiponectin, a protein associated with reduced risk of diabetes and heart disease when present in high levels, increased in the rimonabant arm while decreasing in the placebo group.

The researchers concluded that 57 percent of the improvement in HbA1c were independent of the weight-loss achieved, suggesting that Acomplia directly affected this result.

Side effects most frequently included nausea (experienced by 10.9 percent of patients on Acomplia), nausea (8.7 percent), upper respiratory tract infection (7.2 percent), anxiety (5.8 percent), depressed mood (5.8 percent), and headache (3.8 percent).

The rate of serious adverse effects was 6.5 percent for patients taking Acomplia compared to 3.6 percent on the placebo.

Overall, dropout rates for adverse effects were 9.4 percent for those on Acomplia compared to 2.1 percent on the placebo. The most common adverse effects leading to Acomplia patients leaving the trial were depressed mood disorder, nausea, and paraesthesia (a sensation of tingling, pricking, or numbness of the skin with no apparent physical cause).

"Some current medications for type 2 diabetes are often associated with weight gain," said Dr. Julio Rosenstock of the University of Texas Southwestern Medical School, a researcher in the trial.

"The fact that blood sugar levels were reduced along with weight loss and improvements in HDL-cholesterol and triglycerides may further support the novel mechanism of action of rimonabant, which is different from the mode of action of current oral anti-diabetic medications," Rosenstock said.