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Lipid profile improved with rimonabant
Secondary endpoints from the SERENADE trial presented at ADA meeting.
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CHICAGO – New data demonstrate the efficacy of rimonabant in improving the atherogenic dyslipidemia profile in patients with type 2 diabetes, in addition to reducing weight and improving glycemic control.
Julio Rosenstock, MD, presented the secondary endpoint results on lipid profile from the Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients (SERENADE) at the American Diabetes Association 67th Annual Scientific Sessions.
Rimonabant (Acomplia, Sanofi-Aventis) is the first drug to employ selective blockade of the cannabinoid receptor type 1 and is meant for the treatment of obesity. At a recent FDA Endocrinologic and Metabolic Drugs Advisory Committee meeting, the panel voted unanimously against recommendation of FDA approval of the drug based on psychiatric and neurologic adverse effects. Sanofi-Aventis recently withdrew the new drug application for rimonabant in June.
“Rimonabant may have a role in the overall management of type 2 diabetes in achieving meaningful reductions in HbA1c plus weight loss and improving lipid and adiponectin levels,” Rosenstock, Director of Dallas Diabetes and Endocrine Center at Medical City and clinical professor of medicine, University of Texas Southwestern Medical School, Dallas, said during the oral presentation.
SERENADE trial
SERENADE was a randomized, double blind and placebo-controlled trial. It was designed to assess the effects of rimonabant 20 mg daily compared with placebo in patients with type 2 diabetes (n=278). The study was conducted for a period of six months.
The primary outcome was change in HbA1c level. Early data demonstrated a greater reduction of HbA1c from baseline in patients randomly assigned rimonabant compared with placebo and dietary intervention (0.8% vs. 0.3%; P=.0002). Patients randomly assigned rimonabant also had greater reductions in body weight (6.7 kg vs. 2.8 kg; P<.0001).
However, Rosenstock and colleagues extended the initial analyses of SERENADE and evaluated a secondary outcome of the effects of rimonabant 20 mg on atherogenic dyslipidemia, including changes in non-HDL cholesterol, LDL particle size, adiponectin and the apolipoprotein B–apolipoprotein A-I ratio in the same study population.
They discovered greater increases in HDL in patients randomly assigned rimonabant (10.1% vs. 3.2%; P<.0001). Although changes in LDL were similar between the two treatment groups, LDL particle size was increased in the rimonabant group, which resulted in a reduction of small, dense LDL (0.6% vs. 0%). Patients randomly assigned rimonabant had greater reductions in ApoB/Apo A-I (0.03 vs. 0.002; P=.0045) and increased mean adiponectin levels (1.6 vs. 0.2; P=.0001).
The drug was generally well tolerated in SERENADE, according to Rosenstock.
However, patients randomly assigned rimonabant had a greater proportion of adverse events (70% vs. 57%), including dizziness (10.9% vs. 2.1%) and nausea (8.7% vs. 3.6%).
Psychiatric events were also more common in the patients who received rimonabant, specifically depressed mood (6% vs. 1%) and anxiety (6% vs. 4%).
“Further studies are warranted to explore combinations of rimonabant with other antidiabetic agents so that the risk–benefit profile of cannabinoid receptor 1 blockers on glycemic control plus weight loss in type 2 diabetes can be fully assessed,” Rosenstock said. The benefits of rimonabant on lipid profile, weight loss and glycemic control are currently being tested in the long-term, ongoing CRESCENDO trial. – by Katie Kalvaitis
For more information:
- Rosenstock J, Iranmanesh A, Hollander PA. Improved glycemic control with weight loss plus beneficial effects on atherogenic dyslipidemia with rimonabant in drug-naïve type 2 diabetes: the SERENADE trial. Presented at: The American Diabetes Association 67th Annual Scientific Sessions; June 22-26, 2007; Chicago.