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ADA: Diabetes Prevention Program 15 Years Later

Jun 20, 2014

Findings suggest clinicians can prevent or delay the onset of type 2 diabetes "over a very long period of time"….

In 15 years of follow-up of patients in the landmark Diabetes Prevention Program, lifestyle changes conferred a 27% reduced risk of developing diabetes while metformin conveyed a 17% reduced risk compared with placebo group patients, David Nathan, MD, of Massachusetts General Hospital in Boston, and colleagues reported at the American Diabetes Association meeting.


Nathan said during a press briefing that the findings suggest clinicians can prevent or delay the onset of type 2 diabetes "over a very long period of time."

The main findings of the Diabetes Prevention Program were reported in 2002 in the New England Journal of Medicine. Participants who were at risk of diabetes had been randomized to one of three groups: a lifestyle intervention, preventive metformin, or a placebo group.

The trial showed that the lifestyle intervention reduced the risk of developing diabetes by 58%, while metformin reduced that risk by 31%.

Patients were given the option to continue in an extension of the trial, the Diabetes Prevention Program Outcomes Study (DPPOS). At that point, all arms of the study were allowed to try the lifestyle intervention if they so desired.

Over an average follow-up of 15 years, the researchers found that those in the lifestyle intervention group had 27% lower rate of diabetes than those in the placebo arm, while the metformin group had 17% lower rates of diabetes.

William Knowler, MD, PhD, MPH, of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), said the overall incidence of diabetes was 20% lower in the lifestyle group and 18% lower in the metformin group compared with placebo.

All three groups maintained good glycemic control, with an average HbA1c of 6.1%, 6%, and 6%, respectively, in the placebo, metformin, and lifestyle groups. This was statistically significant but of "questionable clinical impact," Knowler said.

The lack of a major difference could have been a result of the intervention or the rapid diagnosis and intensive treatment of diabetes once it developed, he added.

According to Kieren Mather, MD, of Indiana University, nor were there any differences among the three groups in terms of microvascular complications.

A similar proportion of patients hit the main endpoint of aggregated microvascular complications at 15 years: 12.4% of those on placebo, 13% of those on metformin, and 11.3% of those in the lifestyle group.

However, those who didn’t develop diabetes had a 28% lower risk of microvascular complications than those who did develop diabetes, which implies that that intervening in the prediabetes phase is important in reducing early stage complications, Mather said.

"This equates to a paradox," he said. "We have a reduction in diabetes and a reduced prevalence of complications in those who didn’t develop diabetes, but we don’t have a treatment effect to prevent diabetes complications at this point." He said the achievement of good glycemic control in all three groups may explain the lack of apparent benefit.

Nathan said the finding "provides real hope that acting early and preventing diabetes is going to have good consequences later on."

Nathan explained that over the study period, there were too few cardiovascular events to assess those outcomes, so the researchers instead decided to look at risk factor outcomes, such as changes in lipid and inflammatory markers as well as coronary artery calcification.

In the new analyses, the researchers found that patients in the lifestyle intervention had a greater reduction in cardiovascular risk factors compared with placebo, and that those in the metformin also had a reduced risk but less so than in the lifestyle group.

Nathan said both interventions also offered improvement in coronary artery calcification, with the strongest benefits for men who were taking metformin compared with the other groups.

Nathan said the NIDDK has offered the DPPOS group to apply for more funding and will know soon whether the trial will continue to "follow what we think is an incredibly valuable cohort over time to really pin down what is the early history of diabetes and prediabetes, and what are the even longer-term effects of these interventions in terms of disease."

Practice Pearls:
  • Both lifestyle and metformin reduce the development of diabetes in high-risk patients over a 15 year follow-up period.
  • Both lifestyle and metformin help to prevent diabetes in high-risk patients over the long run, researchers reported here.
  • 50% of the approximately 3000 participants did become diabetic over the time course, "the results show that diabetes is not inevitable in people at high risk.
  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

American Diabetes Association: Nathan DM, et al "Results from the Diabetes Prevention Program Outcomes Study: 1996-2013" ADA 2014.