NIH stops treatment arm in the Look AHEAD Trial: Interpretation and Implications

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Oct 24, 2012, 02:42 ET

SILVER SPRING, Md., Oct. 24, 2012 /PRNewswire-USNewswire/ -- On Friday, October 19, 2012, The National Institutes of Health (NIH), announced the early termination of the treatment being studied in the NIH-funded "Look AHEAD" (Action for Health in Diabetes) trial (http://www.nih.gov/news/health/oct2012/niddk-19.htm). This study was designed to determine if weight loss resulting from a lifestyle change intervention would reduce rates of heart disease, stroke, and cardiovascular-related deaths in overweight and obese adults with type 2 diabetes -a group that is at increased risk for these events. NIH discontinued the lifestyle change intervention after finding no difference in the rates of cardiovascular events such as heart attacks and strokes for participants in the lifestyle intervention group, compared to participants in a diabetes education and support group receiving general health information. The intervention was not stopped because of evidence of harm to either group.

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The Obesity Society (TOS) would like to provide a perspective to better understand and interpret this decision by the NIH.

This landmark study enrolled more than 5,000 overweight and obese patients with diabetes with a planned follow-up period of up to 13 years. Its primary question was whether modest weight loss by such patients via the lifestyle intervention reduced the rate of heart attacks and strokes to a lower level than that seen among similar participants assigned to the diabetes education and support group. All participants received routine medical care from their own healthcare provider.

The trial's Data and Safety Monitoring Board (DSMB) reviewed the data and concluded that there was no difference in the rates of heart attacks and strokes after as many as 11 years of follow-up. Since it was extremely unlikely that a difference would develop with additional follow-up, the NIH, acting on the DSMB's recommendations, determined that the study's primary question had been answered and that the intervention should be stopped. It is noteworthy that the overall rates of heart attacks and strokes among both groups of patients were much lower than had been anticipated.

The ability to monitor the effects of the lifestyle intervention across a wide range of indicators of health and functioning, in addition to the rates of heart attacks and strokes, made the trial a truly unique resource for health care research. The fact that the participants continued to receive the interventions for such a long time added to its value. Although the interventions are discontinued, the trial will continue to monitor the health status of these participants, providing still more valuable information.

While the specific data leading to this decision are not yet publicly available, it is important to recognize that this scaling back of the study does not question the value of weight loss in general.

The science continues to support the idea that losing a modest amount of weight can have substantial health benefits for overweight and obese people, and the Look AHEAD trial has affirmed that for diabetics in particular (www.lookaheadtrial.org). At the 4-year follow-up, lifestyle intervention participants had an average weight loss of 6.2% of their start weight (vs. 0.9% among the diabetes support and education group). They also had greater improvements in diabetes control (and reduced diabetes medications), blood pressure, HDL cholesterol, triglycerides, and fitness and functional mobility. Reports from their earlier follow-ups found greater improvements in quality of life and in sleep apnea. Such benefits are very important for a healthier, more fulfilling life.

Therefore, a distinction should be made about the Look AHEAD study. The study has found that among individuals who are already diabetic, a lifestyle intervention producing moderate weight loss does provide significant health benefits; however, the intervention did not reduce the occurrence of heart attacks or strokes below what was seen in the study's diabetes education and support group. Since the study's primary question had been answered, it was decided to stop the intervention and inform the study participants of the results. It should also be noted that a not dissimilar trial performed among prediabetic patients (Diabetes Prevention Program http://diabetes.niddk.nih.gov/dm/pubs/preventionprogram/#results) demonstrated that weight loss and lifestyle modification reduced the incidence of diabetes during the 10 year follow-up period thus affirming that life style intervention provides a host of other health benefits.

The Look AHEAD trial is a tribute to how the scientific process works. The study was initiated to test a specific hypothesis which appeared intuitive. Scientific conclusions, however, rely on rigorous testing and not intuition. The Look AHEAD trial succeeded in answering the primary questions. TOS applauds this careful approach of the NIH.

In summary, the scaling back of the Look AHEAD trial is not a negative verdict for the benefits of weight loss for people with diabetes or for the population in general. Such benefits remain well documented. Prevention and treatment of obesity and related health conditions are truly complex, and TOS welcomes the scientific evidence gained from this impressive and well-performed trial.

About The Obesity Society
The Obesity Society is the leading scientific society dedicated to the study of obesity. The Obesity Society is committed to encouraging research on the causes, treatment, and prevention of obesity as well as to keeping the scientific community and public informed of new advances in the field. For more information, please visit www.obesity.org.

References
The Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four year results of the Look AHEAD trial . Arch Intern Med. 2010;170(17):1566-1575.

Rejeski J; Ip E; Bertoni A; Bray G; Evans G; Gregg E; Zhang Q and the Look AHEAD Research Group. Lifestyle Change and Mobility in Obese Adults with Type 2 Diabetes. N Engl J Med. 2012 Mar 29;366(13):1209-17.

SOURCE The Obesity Society