In June, the manufacturer withdrew its new drug application to the FDA.
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 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 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, 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-naive type 2 diabetes: the SERENADE trial. Presented
at: The American Diabetes Association 67th Annual Scientific Sessions; June
22-26, 2007; Chicago.