NewsNew Data Shows Acomplia(R) (Rimonabant) Benefited Patients With Type 2 Diabetes by Improving Blood Sugar Control, Reduci
12/05/06 - PRNewswire
CAPE TOWN, South Africa, December 5 /PRNewswire/ --
- First Rimonabant Trial with HbA1c as a Primary Endpoint
Sanofi-aventis announced today that new data on rimonabant,
its first-in-class cannabinoid type 1 (CB1) receptor blocker, showed that
patients with type 2 diabetes not currently treated with anti-diabetic
medications experienced significant improvements in blood sugar control and
weight as well as other risk factors such as HDL-cholesterol (good
cholesterol) and triglycerides when compared to placebo. The study, called
SERENADE, was presented today at the International Diabetes Federation (IDF)
World Diabetes Congress in Cape Town, South Africa. SERENADE is the second
study demonstrating that rimonabant significantly improved blood sugar levels
in people with type 2 diabetes.
In the SERENADE study, treatment-naïve type 2 diabetes patients receiving
rimonabant 20mg per day for a duration of six months significantly lowered
their HbA1c levels by 0.8% from a baseline value of 7.9 as compared to a
reduction of 0.3% in the placebo group (p=0.002). In addition, patients with
an HbA1c level greater than or equal to 8.5% at baseline, significantly
reduced their HbA1c by 1.9% with rimonabant as compared to 0.7% with
placebo(p<0.0009). Over 50% of patients in the rimonabant arm of the trial
achieved HbA1c levels below 7%, the target for good glucose control as
recommended by the American Diabetes Association (ADA)[i]. Importantly, these
improvements in blood glucose control were accompanied by significant and
clinically meaningful reductions in body weight of 6.7 kg (14.8 lbs) in
patients treated with rimonabant 20 mg, while those patients on placebo lost
only 2.7 kg (5.95 lbs) (p<0.0001).
"The management of type 2 diabetes should not only focus on
controlling blood sugar levels but also improve other risk factors such as
weight, good and bad cholesterol, triglycerides and blood pressure," said
Julio Rosenstock, M.D., Director of the Dallas Diabetes and Endocrine Center
at Medical City and also Clinical Professor of Medicine at the University of
Texas Southwestern Medical School, Dallas, Texas who was an investigator in
the SERENADE trial. "This study suggests that rimonabant can achieve
improvement in blood glucose with the added benefit of significant weight
loss and improvement in other risk factors."
Today, more than 194 million adults or 5% of adults worldwide
have been diagnosed with diabetes, with type 2 diabetes constituting 85-95%
of all diabetes in developed countries[ii]. Approximately 90 percent of type
2 diabetes is attributed to people being overweight or obese.[iii] Diabetes
and obesity are often associated with other risk factors for cardiovascular
disease including high blood pressure and unhealthy cholesterol. Worldwide,
diabetes is among the leading causes of blindness, renal failure and lower
limb amputation, as well as death through its effects on cardiovascular
disease (70-80 percent of people with diabetes die of cardiovascular
disease)[ii].
Accompanying the improvements in HbA1c and weight seen in the
rimonabant arm of the SERENADE trial were improvements in multiple
cardiometabolic risk factors. Patients in the rimonabant arm decreased their
waist circumference (a measure of abdominal obesity) by 6.1 cm (2.34 in)
compared to a 2.4 cm (0.93 in) decrease for patients on placebo (p<0.0001).
HDL-cholesterol or "good" cholesterol increased by 10.1% compared to 3.2% for
patients on placebo (p<0.0001). Triglyceride levels (bad fats in the blood)
decreased by 16.3% compared to a 4.4% increase for placebo (p=0.0031). There
was a trend toward reduction in systolic blood pressure by 5 mmHg and
diastolic blood pressure by 1.2 mmHg in the rimonabant 20 mg arm compared to
a 2.2 mm Hg decrease in systolic blood pressure and an increase of 0.1 mm Hg
in diastolic pressure in the placebo arm (p=NS). Fasting Plasma Glucose
decreased by 0.9 mmol/L (16.2 mg/dL) in the rimonabant 20 mg arm compared to
a 0.1 mmol/L (1.8 mg/dL) increase in the placebo arm (p=0.0012). Adiponectin,
a protein associated with reduced risk of diabetes and heart disease when
present in high levels, increased by 1.6 microg/mL in the rimonabant 20 mg
arm compared to a decrease of 0.2 microg/mL in the placebo arm (p=0.0001).
Approximately 57% of the improvements in HbA1C (p<0.001) were
independent of the weight loss achieved, suggesting a direct effect of
rimonabant on this parameter.
The overactivity of the Endocannabinoid System (ECS) in the
fat tissue and muscle is found to promote fat accumulation and decrease
glucose uptake, which can lead to an increased risk of developing insulin
resistance and impaired glucose tolerance. By selectively blocking CB1
receptors of the ECS, which according to animal and human studies can be
found in the brain, fat tissue, gastrointestinal tract, pancreas, liver and
muscle, rimonabant results in a decrease in food intake, a loss of body
weight, and direct improvements in blood sugars (HbA1c), HDL-cholesterol and
triglycerides.
"Some current medications for type 2 diabetes are often
associated with weight gain," said Julio Rosenstock. "The fact that blood
sugar levels were reduced along with weight loss and improvements in
HDL-cholesterol ("good" 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."
The most common side effects with placebo and rimonabant 20 mg
reported in the SERENADE trial were dizziness (2.1% vs. 10.9%), nausea (3.6%
vs. 8.7%), nasopharyngitis (7.9% vs. 7.2%), upper respiratory tract infection
(2.7 % vs. 7.2%), anxiety (3.6% vs. 5.8%), depressed mood (0.7% vs. 5.8%),
and headache (6.4% vs. 3.6%). The rate of serious adverse events was 3.6% for
patients in the placebo arm versus 6.5% for patients in the rimonabant 20 mg.
Overall, discontinuation rates due to adverse events in the
trial were 2.1% in placebo-treated patients versus 9.4% for patients on
rimonabant 20 mg. The most common adverse events leading to discontinuation
for the placebo and rimonabant 20 mg patients, respectively, were nausea (0%
vs. 2.2%), depressed mood disorder (0% vs. 2.2%) and paraesthesia (0% vs.
2.2%).
About SERENADE
SERENADE (Study Evaluating Rimonabant Efficacy in Drug-NAive
DiabEtic Patients) was a multi-centre, randomised, double-blind,
placebo-controlled, parallel-group study comparing rimonabant 20 mg once
daily to placebo in improving blood sugar control (as indicated by HbA1c) in
treatment-naive type 2 diabetic patients not adequately controlled by diet
alone for a period of six months.
The study was conducted on 278 patients at 56 study centres in
the United States, Germany, Argentina, Chile, Hungary, Poland and the
Netherlands. The primary endpoint of the trial was change from baseline of
HbA1c levels. Secondary endpoints included weight and waist circumference, a
key marker of intra-abdominal adiposity, fasting plasma glucose, lipid
parameters and arterial blood pressure.
To be included in the trial patients had to have a diagnosis
of type 2 diabetes for at least two months but less than three years, HbA1c
levels greater than 7% and less than 10%, and could not have been treated
previously with an anti-diabetic medication within six months prior to
screening.
SERENADE is part of an extensive worldwide Phase IIIb clinical
trial programme involving over 22,000 patients in eight studies, which will
investigate the role of rimonabant in the treatment of type 2 diabetes and
cardiovascular disease.
About Rimonabant
In Europe, rimonabant, known as ACOMPLIA(R) is approved as an
adjunct to diet and exercise for the treatment of obese patients
(BMI is greater than or equal to 30kg/m2), or overweight patients
(BMI>27kg/m2) with associated risk factors, such as type 2 diabetes or
dyslipidaemia.
Rimonabant is currently commercialised in the United Kingdom,
Germany, Denmark, Sweden, Finland, Norway, Ireland, Argentina and Austria.
At the end of October 2006, sanofi-aventis submitted a
complete response to the U.S. Food and Drug Administration (FDA) approvable
letter received in February 2006.
About sanofi-aventis
Sanofi-aventis is the world's third largest pharmaceutical
company, ranking number one in Europe. Backed by a world-class R&D
organization, sanofi-aventis is developing leading positions in seven major
therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases,
central nervous system, internal medicine, and vaccines. Sanofi-aventis is
listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Forward Looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995.
Forward-looking statements are statements that are not historical facts.
These statements include financial projections and estimates and their
underlying assumptions, statements regarding plans, objectives and
expectations with respect to future events, operations, products and
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"believes," "intends," "estimates," "plans" and similar expressions. Although
sanofi-aventis' management believes that the expectations reflected in such
forward-looking statements are reasonable, investors are cautioned that
forward-looking information and statements are subject to various risks and
uncertainties, many of which are difficult to predict and generally beyond
the control of sanofi-aventis, that could cause actual results and
developments to differ materially from those expressed in, or implied or
projected by, the forward-looking information and statements. These risks and
uncertainties include those discussed or identified in the public filings
with the SEC and the AMF made by sanofi-aventis, including those listed under
"Risk Factors" and "Cautionary Statement Regarding Forward-Looking
Statements" in sanofi-aventis' annual report on Form 20-F for the year ended
December 31, 2005. Other than as required by applicable law, sanofi-aventis
does not undertake any obligation to update or revise any forward-looking
information or statements.
References:
---------------------------------
[i] American Diabetes Association. Standards of Medical Care in Diabetes
2006. Diabetes Care 2006;29:S4-42.
[ii] The International Diabetes Federation Diabetes Atlas. Available at:
http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC22682A.
Last Accessed November 15th, 2006.
[iii] World Health Organization,
http:www.diabetes.org/diabetes-heart-disease-stroke.jsp. Last accessed
11/17/08 /p2/Line 63-64.