World's Largest Trial of Intensive Glucose Control in Type 2 Diabetes Finds Significant Reduction in Serious

SAN FRANCISCO, CA, Jun 06 (MARKET WIRE) --
The world's largest diabetes trial has shown intensive blood glucose control
in type 2 diabetes reduces the risk of complications -- notably a 21% reduction
in
risk for kidney disease. The study also showed no evidence of any increased
risk of death when blood glucose was intensively controlled, according to
reportspresented here today at the American Diabetes Association's 68th Annual
Scientific Sessions.

"The results clearly demonstrate that intensive control of blood glucose, as
recommended by most current clinical guidelines, has an important role in the
prevention of renal complications of type 2 diabetes. The other major finding
of the trial was that major macrovascular events -- heart attack, stroke and
death from cardiovascular disease -- were not significantly reduced with
intensive glucose control, although there was a trend towards improvement
in these outcomes. However, the results suggest that a multifactorial approach
addressing all the major risk factors including blood pressure and blood lipids
is required to prevent macrovascular disease," said Anushka Patel, MBBS, SM,
PhD,
Study Director of the ADVANCE trial, and Director, Cardiovascular Division, The
GeorgeInstitute for International Health, which conducted the study, in a recent
interview. "The key message is that the study confirms the current approach
that
intensively controlling blood glucose has an important role in the prevention
of the microvascular complications of diabetes."

There was no evidence of an increased risk of death among ADVANCE patients
receiving intensive treatment to lower blood glucose, in contrast to the
similar ACCORD trial in the U.S., which was discontinued prematurely earlier
this
year due to an increased rate of death in its intensive arm.

"Overall, we found that the intensive control strategy reduced the
combinedrisk of macrovascular and microvascular complications by 10%, but that
was
driven largely by the microvascular results," said Dr Patel. "Further,
the14% reduction in microvascular risk was driven mainly by nephropathy
ratherthan retinopathy. We found that intensively controlling blood glucose
reduces
risk of the development or progression of kidney disease by 21%."

ADVANCE did not show a statistically significant effect of intensive glucose
control on cardiovascular disease (10% in the intensively treated group vs.,
10.6% in the standard group). "We believe a protective effect remains plausible
since we were aiming for a 1% difference in A1C levels between the standard and
intensive groups, but achieved an average of a 0.7% difference over the
course of the trial," said Dr. Patel. "Further, the rate of cardiovascular
events
was only 2.2% per year rather than the expected 3% per year, possibly due to
more aggressive treatment of blood pressure and lipids." She also noted that
the wide confidence interval in the trial's results does not exclude the
benefits that epidemiologic evidence predicts.

A1C is a measure of blood glucose over the prior two to three months.

Trial Design

The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and
Diamicron-MR Controlled Evaluation) trial was an international study involving
11,140 high-risk patients with type 2 diabetes based at 214 centers in 20
countries worldwide.

"ADVANCE was designed to address two of the major uncertainties in the
prevention of the vascular complications of diabetes: whether important clinical
benefits would result from reducing A1C to 6.5% or lower and from intensive
blood pressure lowering, whether or not the patient had had hypertension,"
said Stephen MacMahon, DSc, PhD, MPH, Co-Principal Investigator of the study,
Principal Director of The George Institute for International Health. He is
also a Professor of Cardiovascular Medicine and Epidemiology at the University
of
Sydney. In a factorial design, patients received blood-pressure-lowering
treatment with a fixed-dose combination of the angiotensin-converting enzyme
inhibitor perindopril and the diuretic indapamide or a placebo, and diabetes
treatment with gliclazide MR, plus other anti-diabetic drugs as needed.

The average age of participants was 66, with 46% coming from Europe, 37%
from
Asia, 13% from Australia and New Zealand, and 4% from North America. At the
outset, 32% of the participants had already had a cardiovascular event, such as
a stroke
or heart attack, and the balance were already at high risk due to such risk
factors as a history microalbuminuria (protein in the urine), proliferative
diabetic retinopathy, current cigarette smoking, elevated total cholesterol, or
low
HDL (the "good" cholesterol).

"The key objective was to get the intensive group patients down to an A1C of
6.5%, which the trial achieved," said Dr. MacMahon. The investigators did not
have a
particular target for the standard group so they did not have control of what
the standard group would achieve.

"At baseline, the average A1C of all participants was 7.5%," said Dr.
MacMahon. "Physicians treating those in the standard group could give
themany medications they chose according to the guidelines in the local country.

Physicians treating those in the intensive group were required to use
gliclazide MR first and then up to three oral agents, followed by insulin in
order to reach the goal of an A1C of 6.5% or lower. Sulfonylureas,
thiazolidinediones, acarbose, metformin, and insulin were commonly used in
both arms of the study. Aside from gliclazide MR, all medication choices were
left to the treating physician."

"At the end of the five years of follow-up, the average A1C in the intensive
group was 6.5% and in the standard group was 7.3%," he reported. "However, the
average difference in A1C over the course of the trial was 0.7%."

There were two primary outcomes: first, a composite of death and
macrovascular complications -- death, cardiovascular death, nonfatal heart
attacks, and nonfatal stroke; second, a composite of microvascular complications
--
new or worsening renal disease (nephropathy) or diabetic eye disease
(retinopathy). It was prespecified that the outcomes would be analyzed both
jointly and separately.

"As expected, patients in the intensive group had more hypoglycemia
(episodes of low
blood glucose), but the overall incidence was actually quite low," he said. The
incidence of severe hypoglycemic events was 2.7% in the intensive group and
1.5% in the standard group, and this difference was statistically significant.

Translating the Results to Action

"It's more challenging today than it has ever been in the past to
demonstrate a benefit for glucose control first because the standard group was
in such good control. Patients getting standard treatment are already in good
glycemic control today and are also getting good treatments for cholesterol
and blood pressure and are getting aspirin," said Dr. MacMahon. "So the overall
rate of heart attacks is low, which means we might need a much larger group
and a much longer study to detect the effects of glucose lowering on
macrovascular outcomes."

"If there is any effect of glucose control using currently available drugs
on
heart attacks, it's going to be small, and therefore the key message with heart
attacks and strokes is that diabetes patients need comprehensive treatment to
control
all risk factors including blood pressure and cholesterol," said Dr. MacMahon.

Nearly 21 million Americans have diabetes, a group of serious diseases
characterized by high blood glucose levels that result from defects in the
body's ability to produce and/or use insulin. Diabetes can lead to severely
debilitating or fatal complications, such as heart disease, blindness, kidney
disease, and amputations. It is the fifth leading cause of death by disease in
the United States. Type 2 diabetes involves insulin resistance -- the body's
inability to properly use its own insulin. Type 2 used to occur mainly in
adults who were overweight and ages 40 and older. Now, as more children and
adolescents in the United States become overweight and inactive, type 2 diabetes
is occurring more often in young people. Globally, there are approximately 250
million people with diabetes, and that number is estimated to rise to 380
million in 2025.

Results of the blood pressure component of the trial, already published in
the Lancet in September 2007 showed that a fixed combination of
perindopriland indapamide given to patients with type 2 diabetes, regardless of
baseline blood pressure, reduced the risks of vascular events by 9% over the
course of five years. The relative risk of cardiovascular death was reduced
by 18%.

ADVANCE was designed, conducted, monitored, analyzed and reported by an
international collaborative medical research group. The study was led by
The George Institute for International Health, funded by the Australian
Government's
National Health and Medical Research Council and by Servier, and carried out
independently of the government and industry sponsors.

The George Institute for International Health seeks to improve the health of
millions of people worldwide by providing the best research evidence to
guide global health decisions and applying this research to health policy and
practice. The George Institute is a leader in clinical trials, health policy and
capacity-building areas and works in collaboration with medical institutions
around the world.

The American Diabetes Association is the nation's leading voluntary health
organization supporting diabetes research, information and advocacy. Founded in
1940, the Association has offices in every region of the country, providing
services to hundreds of communities. For more information, please call the
American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit
www.diabetes.org.Information from both these sources is available in English and
Spanish.

Symposium, Friday, 2:00 pm PDT

NOTE TO EDITOR:

Visit http://www.diabetes.org/adablog to read blog posts from the
Association's Scientific Sessions from former USA Today reporter,
Anita
Manning.

The George Institute for International Health
Emma Orpilla
+61410 411 983/eorpilla@george.org.au

Contact:
Diane Tuncer
(703) 299-5510
Colleen Fogarty
(703) 549-1500 ext. 2146

NEWS ROOM: June 6-10, 2008
Room 250, Moscone Convention Center
(415) 978-3508
Fax: (415) 978-3524

Copyright 2008, Market Wire, All rights reserved.

-0-