74th Scientific Sessions of the American Diabetes Association (ADA):
Diabetes Prevention Program Outcomes Study (DPPOS) Highlights
EndocrineWeb.com summarizes some of the results of the Diabetes Prevention Program Outcomes Study (DPPOS) featured during the American Diabetes Association’s 74th Scientific Sessions held at the Moscone Center June 13-17, 2014 in San Francisco.
The DPPOS data is timely, as the Centers for Disease Control and Prevention (CDC) just revealed that 29 million people in the United States (US) have diabetes. Approximately, 28 million of those individuals have Type 2 Diabetes (T2D). The incidence of new T2D cases per annum amounts to 1.7 million. Furthermore, the CDC’s report indicates that 86 million people in the US are prediabetic and at increased risk for developing T2D over time.
Diabetes Prevention Program (DPP)
The Diabetes Prevention Program was a multicenter trial with 27 centers in the US. “The DPP was designed to determine whether the development of diabetes could be prevented or delayed in persons of high-risk and very high risk,” stated David M. Nathan, MD, Chairman of the DPP/DPPOS and Professor of Medicine at Harvard Medical School in Boston. At baseline, each volunteers’ glucose levels were elevated (prediabetes), and they all were overweight or obese. The study population represented racial, ethnic and age groups often affected by T2D.
Two study interventions were compared:
- Lifestyle intervention group: behavioral modification aimed at reducing weight by 7%.
- Active treatment group: metformin was used to prevent diabetes, not treat it.
The DPPOS, in follow-up to the DPP, was designed to determine if the development of diabetes demonstrated in the DPP study—which was delayed over a brief time period— would continue to be delayed or prevented over a longer time period, as well as the health and economic implications. Furthermore, it was important to quantify the effects of the prevention or delay of diabetes on macro- and micro-vascular complications. The DPPOS studied the earliest stages of diabetes complications, which includes blindness, kidney disease, heart disease, and stroke.
Throughout the DPPOS, lifestyle lessons were provided for the original lifestyle group, and metformin was given to the original metformin group. “During DPPOS, the annual diabetes incidence rates in the original, placebo, and metformin groups declined to approximately equal the rates in the lifestyle group, which remained remarkably stable at approximately 5% per year over time,” stated William Knowler, MD, PhD, MPH. Dr. Knowler is Chief, Diabetes Epidemiology and Clinical Research at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which provided funding for the study. Furthermore, Dr. Knowler explained, “The reasons for this decline are not clear. Despite the convergence of the annual diabetes incidence rates and long-term follow-up, the differences between groups attained in the first three years resulted in continued lower overall long-term incidence of diabetes over the 15 years of follow-up, during which the diabetes incidence rate overall was 18% lower in the metformin group and 20% lower in the original lifestyle group than in the original placebo group.”
Although diabetes delay or prevention was substantial with lifestyle training or metformin over 15 years, all treatment groups maintained good glycemic control. The averages of HbA1C and the index of chronic glucose levels over the follow-up period were 6.0% (lifestyle group) 6.0% (metformin group), and 6.1% (placebo group). While the differences are small, “The good news is that all three groups maintained good glycemic control on average, perhaps not only as a result of our interventions, but as a result of rapid diagnosis and intensive treatment of diabetes once it developed,” stated Dr. Knowler.
Implications on Microvascular Complications
“The main result was that the average microvascular disease prevalence in year 15 follow-up, after DPP randomization: 12.4% prevalence in the placebo group, 11.3% prevalence in the lifestyle group, and 13% in the metformin group. This difference was not statistically significant,” indicated Dr. Kieren Mather. Dr. Mather is Professor of Medicine at Indiana University School of Medicine in Indianapolis, Indiana.
- The mean prevalence of microvascular endpoints was higher in men than in women—about 50% higher.
- The prevalence rate for the placebo and metformin groups were about 11% for the aggregate microvascular outcome; whereas, it was about 8% for the lifestyle participants, which equates to ~21% reduction in the prevalence of microvascular complications in the female subgroup.
- In all three groups, there was a significant difference in the microvascular disease prevalence at year 15 in volunteers who progressed to diabetes compared to those who did not progress to diabetes: 13% prevalence vs ~10% prevalence, equating to a 27% lower prevalence in volunteers who had not progressed to diabetes.
In response to the above outcomes, Dr. Mather said, “The relevant factor seemed to be whether you had progressed to diabetes rather than any feature of the original treatment design. This equates to a paradox. We have diabetes reduction, and we have a reduced prevalence of complications in those who did not develop diabetes compared to those who did, but we don’t have a treatment effect to prevent diabetes complications at this point.”
Public Health Implications
Dr. Judy Fradkin, MD, Director of NIDDK, Division of Diabetes, Endocrinology and Metabolic Diseases summarized the implications of the DPP/DPPOS studies on public health. “As a result of this study, YMCAs across the country have developed programs to try to deliver the DPP interventions cost-effectively. Congress has established a national diabetes prevention program, which is being administered by the CDC,” said Dr. Fradkin. Furthermore, Dr. Fradkin invited the investigators to submit an application for another 10 years of support so the volunteers can be followed into the period of time when they may develop more serious complications from diabetes.