Boston, MA - Long-awaited final results of the Diabetes Prevention Program (DPP) show a dramatic 58% reduction in new type 2 diabetes with an intensive lifestyle intervention focused on weight loss, and a 31% reduction with metformin (Glucophage® - Bristol-Myers Squibb) treatment, among subjects at high risk for developing the disease. The report, from the Diabetes Prevention Program Research Group, is published in the February 7, 2002 issue of the New England Journal of Medicine.
The group's findings suggest these strategies represent two "highly effective" means of preventing type 2 diabetes, the researchers write. They estimate about 10 million Americans resemble DPP participants in terms of their age, BMI, and glucose concentrations. "If the study's interventions were implemented among these people, there would be a substantial reduction in the incidence of diabetes," they write.Reimbursement for lifestyle interventions?
"The lifestyle intervention was particularly effective, with one case of diabetes prevented per seven persons treated for 3 years," the authors, led by Dr William Knowler (National Institute of Diabetes and Digestive and Kidney Diseases), write. (In order to prevent one case of diabetes, 13.9 patients would have to receive metformin for 3 years.)
"Thus, it should also be possible to delay or prevent the development of complications, substantially reducing the individual and public health burden of the disease," Knowler et al conclude.
The success of the lifestyle modification arm in this trial raises again the thorny issue of who pays for preventive intervention. "I would certainly recommend that people who are at high risk for type 2 diabetes be offered a lifestyle intervention program similar to what we provided," Knowler told heartwire in an interview.
"The difficulty of course is that most healthcare organizations or practices are really not organized to provide this sort of intervention, or in many cases, may not pay for this kind of intervention," Knowler added. "That's something healthcare organizations and insurance companies I hope will address on the basis of this paper - making policy decisions towards supporting this kind of treatment for people at high risk of diabetes."
Several groups, including the NIDDK, the American Diabetes Association (ADA), the Centers for Disease Control and Prevention, and the Indian Health Service, all of which supported in part this investigation, have appointed panels to make recommendations on implementation of these findings, Knowler said. The study was also supported by the NIH, among others.
The results reported from the DPP mirror those from the Finnish Diabetes Prevention Study. In that study, first presented at the 60th Scientific Sessions of the American Diabetes Association in 2000, and subsequently published during 2001 in the New England Journal of Medicine, a similar intensive lifestyle intervention produced a 58% reduction in new diabetes among high-risk subjects.
Dr Nathaniel Clark (Vice President for Clinical Affairs, ADA) told heartwire he was impressed by the changes in risk associated with relatively modest weight loss in this study (average loss in the intervention group was 5.6 kg). However, he said, "even though the changes were modest, most people can't do this easily. I think the challenge will be that the intervention that was made to get these people to lose the weight and to exercise was really enormous and very costly."
The question will be whether other ways might be found to accomplish similar goals without the cost, Clark said. "If we can, that will be great news; if we can't, then to some degree the power of the study will be somewhat lost. Time will tell."
The ADA hopes though, that convincing data such as the DPP and Finnish DPS results, will help show that reimbursement should be given for nutritional and exercise therapy, Clark added. Recently, there has been coverage granted for medical nutritional therapy for patients with diabetes, he said, "and that was an enormous step forward. Now we have to move ahead, and say, based on these studies, can we get agreement for prevention of diabetes?"Identical results to Finnish DPS
Investigation into risk factors for type 2 diabetes have shown increased risk for the disease associated with factors such as overweight, a sedentary lifestyle, and elevated plasma glucose concentrations, both in the fasting state and after an oral glucose load, the researchers point out. All of these factors can be affected by intervention, they reasoned, and might reduce the development of type 2 diabetes among subjects at risk.
The DPP project enrolled 3234 subjects at risk for type 2 diabetes by virtue of overweight (BMI > 24; > 22 in Asians) and a plasma glucose concentration of 95-125 mg/dL in the fasting state, and 140-199 mg/dL 2 hours after an oral glucose load, levels considered elevated, but not diagnostic of diabetes by ADA criteria. Individuals from a variety of ethnic backgrounds were enrolled: participants were 54.7% Caucasian, 19.9% African American, 15.7% Hispanic, 5.3% American Indian, 4.4% Asian. The average age of subjects was 51 years, and 68% were women.
They were randomized to one of three groups: standard lifestyle recommendations and metformin (850 mg) or placebo twice daily, or an intensive program of lifestyle modification. Metformin, a biguanide antihyperglycemic agent, is already used to treat type 2 diabetes. (A fourth DPP arm, studying troglitazone [Rezulin®, Warner-Lambert] was discontinued in 1998 due to potential liver toxicity from the drug, which was subsequently pulled from the market.)
Subjects assigned to intensive lifestyle modification had as their goal the achievement and maintainance of weight loss of at least 7% of their initial body weight, by adopting a healthy diet low in calories and fat, and by increasing moderate-intensity physical activity, such as brisk walking, to a minimum of 150 minutes per week. They also participated in a 16-lesson curriculum on diet, exercise and behavior modification, taught on a one-to-one basis by a case manager over the first 24 weeks, with follow-up group and individual sessions, usually monthly. The primary endpoint was diabetes.Results apply to ethnically and culturally diverse population
After an average 2.8 years of follow-up, the lifestyle intervention was found to reduce the incidence of diabetes by 58% (95% CI 48-66%), and metformin by 31% (95% CI 17-43%).
DPP: Incidence of type 2 diabetes (cases per 100 person-years)
Lifestyle modification group
The average weight loss was 0.1, 2.1, and 5.6 kg in the placebo, metformin, and lifestyle modification groups respectively. In terms of adverse events, rates of hospitalization and mortality were similar between the groups; the rate of gastrointestinal symptoms was highest with metformin, and the rate of musculoskeletal symptoms was highest with the lifestyle intervention.
"The results of our study extend previous data showing that lifestyle interventions can reduce the incidence of diabetes, and demonstrate the applicability of this finding to the ethnically and culturally diverse population of the United States," the researchers conclude.
DPP investigators will continue to follow subjects to see whether glucose levels can be maintained over time below levels diagnostic of diabetes, and whether long-term outcomes are improved, they write. They will also be publishing in future on secondary outcomes, including reductions in risk factors for cardiovascular disease, and in the proportions of patients with atherosclerosis or cardiovascular disease.
Heartwire from Medscape © 2002
Cite this: Diabetes Prevention Program: Lifestyle change, metformin treatment prevent progression to type 2 diabetes - Medscape - Feb 06, 2002.