A Decade Later, Lifestyle Changes or Metformin Still Lower Type 2 Diabetes Risk

Study reports on persistence of benefits seen in the Diabetes Prevention
Program

Intensive lifestyle changes aimed at modest weight loss reduced the rate of
developing type 2 diabetes by 34 percent compared with placebo in people at
high risk for the disease, researchers conclude based on 10 years of data.

Participants randomly assigned to make lifestyle changes also had more
favorable cardiovascular risk factors, including lower blood pressure and
triglyceride levels, despite taking fewer drugs to control their heart disease
risk, according to the study.

Treatment with the oral diabetes drug metformin reduced the rate of developing
diabetes by 18 percent after 10 years compared with placebo. Results of the
Diabetes Prevention Program Outcomes Study (DPPOS), which examines the
persistence of the interventions tested in the Diabetes Prevention Program
(DPP), appear online in The Lancet on Oct. 29, 2009.

"In 10 years, participants in the lifestyle changes group delayed type 2
diabetes by about four years compared with placebo, and those in the metformin
group delayed it by two years. The benefits of intensive lifestyle changes
were especially pronounced in the elderly. People age 60 and older lowered
their rate of developing type 2 diabetes in the next 10 years by about half,"
said study chair David M. Nathan, M.D., of Massachusetts General Hospital.

In the United States, about 11 percent of adults--24 million people--have
diabetes, and up to 95 percent of them have type 2 diabetes. An additional 57
million overweight adults have glucose levels that are higher than normal but
not yet in the diabetic range, a condition that substantially raises the risk
of a heart attack or stroke and of developing type 2 diabetes in the next 10
years. "The spiraling epidemics of obesity and type 2 diabetes in United
States and worldwide show no signs of abating," said Griffin P. Rodgers, M.D.,
director of the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), part of the National Institutes of Health. "Millions of
people could delay diabetes for years and possibly prevent the disease
altogether if they lost a modest amount of weight through diet and increased
physical activity."

The DPPOS is a continuation of the DPP, a large, randomized trial in 3,234
overweight or obese adults with elevated blood glucose levels. Researchers
announced the initial findings of the DPP in 2001, a year earlier than
scheduled because results were so clear: after three years, intensive
lifestyle changes reduced the development of type 2 diabetes by 58 percent
compared with placebo. Metformin (850 milligrams twice a day) reduced it by
31 percent compared with placebo.

Striking as the findings were, the researchers could not say how long the
benefit would endure, since the results were based on just three years of
data. After a bridge period from January to July 2002, when all participants
learned the results and were offered a 16-session program explaining how to
make intensive lifestyle changes, the DPPOS began, with 88 percent of DPP
volunteers taking part.

Intensive lifestyle changes consisted of lowering fat and calories in the diet
and increasing regular physical activity to 150 minutes per week.
Participants received training in diet, exercise (most chose walking), and
behavior modification skills. In the first year of the DPP, this group lost
15 lbs. on average but regained all but about 5 pounds over 10 years. The
metformin group has maintained a loss of about 5 pounds, and the placebo group
lost less than 2 pounds over the decade.

About 5 to 6 percent of those in the lifestyle intervention group developed
type 2 diabetes annually, an incidence rate that remained steady throughout
the DPPOS. When the DPP ended in 2001, the metformin and placebo groups were
developing diabetes at the rate of 8 and 11 percent a year, respectively. In
10 years, however, the yearly diabetes incidence rates for the drug and
placebo groups had also fallen to about 5 to 6 percent, and the lifestyle
intervention group's rate remained at this lower level.

The researchers are looking at a number of explanations for the convergence of
diabetes incidence rates for the three groups. One may be that lifestyle
changes adopted by the drug and placebo groups after the DPP ended may have
lowered their rate of type 2 diabetes over time.

"Sustaining even modest weight loss with lifestyle changes is highly
challenging, but it produced major long-term health rewards by lowering the
risk of type 2 diabetes and reducing other cardiovascular risk factors in
people at high risk of developing diabetes," said lead author and a principal
investigator for the study, William Knowler, M.D., Dr.P.H., of the NIDDK in
Phoenix. "Once we learned how dramatically this intervention reduced diabetes
onset in the DPP, we offered modified training in lifestyle changes to all
participants, which probably contributed to the falling diabetes rates in the
placebo and metformin groups."

At enrollment in the DPP, participants ranged from age 25 to 85 years, with an
average age of 51. Their average body mass index (BMI) was 34, which is in
the obese range. BMI measures weight in relation to height. Forty-five
percent of participants were from minority groups disproportionately affected
by type 2 diabetes: African-Americans, Hispanic/Latino Americans, American
Indians, and Asian-Americans and Pacific Islanders. The trial also recruited
other groups at higher risk for type 2 diabetes, including people age 60 years
and older, women with a history of gestational diabetes, and people with a
first-degree relative with type 2 diabetes.

Other studies have shown that diet and exercise delay type 2 diabetes in
at-risk people. However, the DPP, conducted at 27 centers nationwide
(www.bsc.gwu.edu/dpp/clinics.htmlvdoc), was the first major trial to show that
lifestyle changes can effectively delay diabetes in a diverse population of
overweight American adults at high risk of diabetes. Questions and Answers
about the DPP/DPPOS will be available at
www2.niddk.nih.gov/Research/ClinicalResearch/DPPOS.

About 24 million people in the United States have diabetes. It is the main
cause of kidney failure, limb amputations, and new onset blindness in adults
and a major cause of heart disease and stroke. Type 2 diabetes, which accounts
for up to 95 percent of all diabetes cases, becomes more common with
increasing age. It is strongly associated with obesity, inactivity, family
history of diabetes, history of gestational diabetes, impaired glucose
metabolism, and racial or ethnic background. The prevalence of diagnosed
diabetes has more than doubled in the last 30 years, due in large part to the
upsurge in obesity.

The National Diabetes Education Program, jointly sponsored by the NIH, the
Centers for Disease Control and Prevention, and 200 partner organizations,
provides diabetes education to improve the treatment and outcomes for people
with diabetes, promote early diagnosis, and prevent or delay the onset of
diabetes. In its "Small Steps. Big Rewards. Prevent Type 2 Diabetes"
campaign, the NDEP (www.ndep.nih.gov) explains how people at risk can take
steps to turn the tide against this disease.

The DPP is registered as NCT00004992, and the DPPOS is registered as
NCT00038727 in clinicaltrials.gov. The studies have been funded by the
National Institute of Diabetes and Digestive and Kidney Diseases; Eunice
Kennedy Shriver National Institute of Child Health and Human Development;
National Institute on Aging; National Eye Institute; National Heart, Lung, and
Blood Institute; National Center on Minority Health and Health Disparities;
National Center for Research Resources; and Office of Research on Women's
Health within the NIH. Additional funding came from the Indian Health
Service, the Centers for Disease Control and Prevention, and the American
Diabetes Association. Lipha (Merck-Sante) provided medication. LifeScan
Inc.; Merck-Medco Managed Care, Inc.; and Merck and Co. donated materials,
equipment, or medicines.

NIDDK, part of the NIH, conducts and supports basic and clinical research and
research training on some of the most common, severe and disabling conditions
affecting Americans. The Institute's research interests include diabetes and
other endocrine and metabolic diseases; digestive diseases, nutrition, and
obesity; and kidney, urologic and hematologic diseases. For more information,
visit www.niddk.nih.gov.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency
- includes 27 Institutes and Centers and is a component of the U.S. Department
of Health and Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research, and it
investigates the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit www.nih.gov.

Note to Media: To interview David M. Nathan, M.D., DPP/DPPOS Study Chair,
contact Sue McGreevey, 617-724-2764, SMcgreevey@partners.org. To interview
lead author William Knowler, M.D., Dr.P.H., NIDDK, contact the NIDDK Office of
Communications and Public Liaison, 301-496-3583, niddkmedia@mail.nih.gov.

For Broadcast Media: A bites/b-roll package with sound bites from Dr. David
Nathan, DPP/DPPOS study chair, Dr. Griffin P. Rodgers, NIDDK Director, and
study participants will be available at
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/PRNewswire -- Oct. 28/

SOURCE National Institutes of Health