Questions & Answers about the Diabetes Prevention Program Outcomes Study
What is the Diabetes Prevention Program (DPP)?
The DPP was a randomized, controlled clinical trial that determined if certain interventions could prevent or delay type 2 diabetes in adults at high risk for developing the disease. The multicenter study enrolled 3,234 overweight participants with blood glucose levels that were higher than normal but not yet in the diabetic range. Forty-five percent of participants were from minority groups disproportionately affected by type 2 diabetes: African Americans, Hispanic Americans, Asian Americans and Pacific Islanders, and American Indians. The trial also recruited other groups at higher risk for type 2 diabetes, including individuals age 60 and older, women with a history of gestational diabetes, and people who have a first-degree relative with type 2 diabetes.
What interventions were tested in the DPP?
Participants were randomly assigned to one of the following approaches:
- Intensive lifestyle changes with the aim of reducing weight by 7 percent through a low-fat diet and increased physical activity. Participants were asked to maintain physical activity at least 150 minutes a week with moderate exercise, such as walking or biking.
- Standard advice on diet and exercise plus treatment with the drug metformin (850 mg twice a day), approved in 1995 to treat type 2 diabetes.
- Standard advice on diet and exercise plus placebo pills in place of metformin.
A fourth arm of the study, treatment with the drug troglitazone (Rezulin) combined with standard diet and exercise recommendations, was discontinued in June 1998 due to the potential for liver toxicity.
What instruction was provided to the lifestyle changes group?
In the DPP, participants received instruction in diet, exercise, and behavior modification. Case managers met with each participant for at least 16 sessions in the first 24 weeks and then at least every other month individually or in groups. Participants were asked to lower fat to less than 25 percent of caloric intake. If reducing fat did not result in weight loss, a calorie goal was added. Participants received culturally sensitive instruction in diet, exercise, self-monitoring, goal-setting, and problem-solving. The lifestyle materials are available for educational purposes on the DPP web site.
What were the DPP’s main findings?
After about 3 years of follow-up, participants randomly assigned to intensive lifestyle changes reduced the development of type 2 diabetes by 58 percent compared with placebo. Metformin (850 mg twice a day) lowered diabetes incidence by 31 percent compared with placebo. For more information, see the Diabetes Prevention Program Fact Sheet. For a list of scientific publications by DPP researchers, see the DPP/Diabetes Prevention Program Outcomes Study (DPPOS) Study web site.
How did the DPP transition to the DPPOS?
After the main study results were explained to participants, the placebo and metformin groups learned about their treatment assignments and stopped taking the drug and the placebo pill for 2 weeks. The study offered all participants, including those who had developed diabetes, instruction in making lifestyle changes. The instruction consisted of a 16-session group program modeled after the training given to lifestyle changes participants in the DPP. The DPPOS began in September 2002. Those randomly assigned to metformin continued taking 850 mg of the drug twice a day unless diabetes developed and required other types of treatment or the drug was discontinued for other reasons. Those assigned to placebo stopped taking the placebo pill.
What is the DPPOS?
The DPPOS aims to assess the long-term effects of interventions used in the DPP on the development of type 2 diabetes and its complications. Eighty-eight percent of all surviving DPP participants who were eligible joined the DPPOS.
What are the main findings of the DPPOS?
After an average of 10 years’ follow up, intensive lifestyle changes aimed at modest weight loss
- reduced the rate of developing type 2 diabetes by 34 percent compared with placebo.
- reduced the rate of developing type 2 diabetes by 49 percent in those age 60 and older compared with placebo.
- delayed type 2 diabetes by about 4 years compared with placebo.
- reduced cardiovascular risk factors.
- reduced hemoglobin A1c (A1C) and fasting glucose compared with placebo. The A1C test gives information about average blood glucose levels for the past 2 to 3 months.
After an average of 10 years’ follow up, treatment with metformin
- reduced the rate of developing diabetes by 18 percent compared with placebo.
- delayed diabetes by 2 years compared with placebo.
- reduced A1C and fasting glucose compared with placebo.
What tests were used to determine if a person was at high risk for developing type 2 diabetes?
DPP researchers used the fasting blood glucose test (FBG) and the oral glucose tolerance test (OGTT) to identify those at high risk for type 2 diabetes. All DPP participants were overweight and had high fasting blood glucose levels and 2-hour OGTT readings, but they did not have diabetes at the start of the study.
- In the FBG test, blood glucose is measured after an 8-hour fast, usually overnight.
- In the OGTT, blood glucose is measured after an 8-hour fast and 2 hours after an individual drinks a sweet beverage. The OGTT gives more information about blood glucose abnormalities than a single test, such as the more common, less expensive FBG test.
What percentage of participants in the different groups developed type 2 diabetes during the 10 years of follow-up?
On average, about 8 percent of those in the placebo group developed type 2 diabetes annually, while 6 percent in the metformin group and 5 percent in the lifestyle changes group developed type 2 diabetes annually. Over the 10-year period, metformin and lifestyle intervention reduced the development of diabetes by 18 percent and 34 percent, respectively.
Is metformin approved by the Food and Drug Administration (FDA) to prevent type 2 diabetes?
The FDA has not approved any drugs to prevent type 2 diabetes. Metformin is approved as an oral medication to treat type 2 diabetes but is not currently approved to prevent the disease.
How do the DPP/DPPOS results compare to the findings of other type 2 diabetes prevention studies?
Other studies have examined the effects of intensive changes in diet and exercise in people at risk for type 2 diabetes. A study in Finland showed that diet and exercise resulted in a risk reduction similar to that shown in the DPP/DPPOS. However, the Finnish trial did not study the effects of metformin nor did it examine the effects of lifestyle changes in specific subgroups by weight, age, or race/ethnicity. In addition, participants in the Finnish study were a fairly homogenous European population compared with DPP volunteers, who come from diverse age and racial/ethnic groups. Cultural factors greatly influence lifestyle changes. It was important to show that type 2 diabetes can be prevented in U.S. minority populations that are at disproportionate risk.
How do diet and physical activity prevent diabetes?
Obesity and sedentary lifestyle are known to increase the risk of both insulin resistance and type 2 diabetes. Insulin resistance, a disorder in which target tissues--muscle, fat, and liver cells--fail to use insulin effectively, accompanies and usually precedes type 2 diabetes. With the onset of insulin resistance, the pancreas compensates by producing more insulin, but gradually its capacity to secrete insulin in response to meals falters, and the timing of insulin secretion becomes abnormal. Weight loss from diet and increased physical activity may lower diabetes risk by improving the ability of muscle cells to use insulin and to handle glucose more efficiently.
Lifestyle changes with diet and exercise reduced diabetes risk, as did treatment with metformin. By combining these interventions, could diabetes risk be reduced even further?
The DPPOS did not study the combination of lifestyle changes and metformin, so the researchers cannot answer this question directly. However, an overseas study found no additional benefit in combining these two interventions.
Do the DPP interventions affect the risk of cardiovascular disease, an important cause of mortality in people with type 2 diabetes?
During 10 years of follow up, those randomly assigned to lifestyle changes improved cardiovascular risk factors compared with the placebo group. For example, they had lower blood pressure levels and lower triglyceride levels, despite taking fewer drugs for these conditions. The DPPOS will determine whether the differences in cardiovascular risk factors translate into differences in cardiovascular disease over time.
How many people in the United States are at risk for type 2 diabetes? Would the DPP interventions benefit all of them?
The CDC estimates that about 57 million adults age 20 years and older have impaired fasting glucose or impaired glucose tolerance or both. Most researchers and clinicians think it is reasonable to assume that most people with these conditions would benefit from the interventions tested in the DPP.
What is being done to inform the public and health care professionals about the results of this clinical trial?
In 2002, the National Diabetes Education Program (NDEP), jointly sponsored by the National Institutes of Health and the Centers for Disease Control and Prevention, launched a comprehensive prevention initiative, Small Steps. Big Rewards. Prevent Type 2 Diabetes, to translate the results of the DPP Study into public health practices (https://www.niddk.nih.gov/health-information/communication-programs/ndep/about-national-diabetes-education-program). It was the nation's first comprehensive campaign to stem the diabetes epidemic by reaching out to the millions of Americans at high risk for type 2 diabetes. The campaign delivers practical, real-world tools to help people--from women with a history of gestational diabetes and their children to older adults--take the small steps needed to achieve the big reward of preventing or delaying type 2 diabetes. NDEP also produces materials for the full health care team responsible for helping people at risk prevent or delay type 2 diabetes (https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-education-outreach).
As a result of the DPPOS findings, NDEP will refresh the Small Steps. Big Rewards campaign with new information and reiterate, for all audiences, the importance of modest weight loss as a result of increasing physical activity and making healthy food choices. The continuing outreach will include presentations at scientific and medical meetings, culturally appropriate messages and materials for audiences at higher risk of developing diabetes, public service advertising and media relations outreach, and the full engagement of the 200 partner organizations that work closely with NDEP to help promote the latest messages.
Will the DPPOS continue?
The DPPOS is scheduled to follow participants for 5 more years to learn more about the effects of these interventions on the development of type 2 diabetes and its complications.
What happened to the volunteers who developed diabetes?
Those whose developed diabetes remain in the DPPOS. If good blood glucose control could not be maintained by the DPP or DPPOS interventions, (i.e., if A1C was 7 percent or higher), they were referred to their own physicians for further care.
Are diet and exercise beneficial even after diabetes develops?
Research has clearly shown that diet and exercise help people with type 2 diabetes control their blood glucose, blood pressure, and blood lipids in the short term. Although diet and exercise should lower the risk of developing cardiovascular disease and the other complications of diabetes, no long-term clinical trials have addressed this question. The NIH-funded Look AHEAD (Action for Health in Diabetes) study is examining how diet and exercise affect heart attack, stroke, and cardiovascular-related death in people with type 2 diabetes.