Hi. I am Dr. Anne Peters from the University of Southern California, and I am here today to discuss why the Look AHEAD trial was stopped. I am one of the principal investigators of the Look AHEAD trial, so I know the trial pretty well. From my perspective, it has been a very interesting study, and I think that we have interesting findings to come that may not be reflected in what has been learned recently.

The Look AHEAD trial looked at the benefits of weight loss and exercise in the treatment of type 2 diabetes.^[1] I can tell you from the outset that we were successful. We got our patients to lose weight, increase their physical activity, and do it over a long period of time — for up to 11 years. I think that is important: We were able to reach our lifestyle goals. But the primary outcome of this study was a macrovascular event outcome. It consisted of nonfatal myocardial infarction, nonfatal stroke, death, or hospitalization for angina. In terms of the primary outcome, we did not see a difference between the 2 groups at 11 years.

Overall, the rates of cardiovascular events and death were actually quite low in both the intervention group and the control group. We did not see a difference in the lifestyle arm even though they did better in terms of weight loss and increased physical activity. There was, however, only 1 outcome. I believe that there are many other outcomes that people derived along the way from losing weight and becoming more physically active. For instance, we know that rates of sleep apnea were lower in the group that was intensively treated. We know that patients had lower rates of urinary incontinence and they were on less medication. There are many things that we need to analyze further in order to fully look at the benefits of weight loss and exercise in this population, but we do know that they did not improve the 1 big macrovascular primary outcome. We also need to look at subsets; there may be people who did better or worse in terms of responding to the intervention. All of these analyses (although I want them all done right away) have not been finished yet. I think that there is a lot that we have to do to truly look at all the benefits and risks of a lifestyle intervention. Those are the headlines. Let me go into the details to explain a little more.

This study consisted of 5145 adults with type 2 diabetes who had a body mass index (BMI) > 25. They were overweight when they came in to the study and were randomly assigned to the intensive lifestyle arm or the diabetes support and education (DSE) arm, which was, in essence, the control group who were given education and meetings twice a year, but they were not given the intervention that we provided to the lifestyle group. The intensive lifestyle group had a wonderful intervention: They were given individual sessions with a nutritionist and/or a trainer, they had group sessions, they had refresher courses, and they were given all the tools they needed to really work on and succeed at their lifestyle intervention. I think our patients did a fantastic job, and we were able to see an 8.6% reduction in body weight in the first year. That was not entirely sustained. During the next year, that weight loss changed to only about 5% of their body weight, but that was maintained through the duration of the trial to 11 years. We were able to show that we could produce modest weight loss and improve physical activity over time in these individuals with type 2 diabetes. However, what we did not show was a reduction in cardiovascular events and death.

When you start talking to your patients about this trial, it does not mean that they should go out and eat anything they want and stop exercising. Again, there are real benefits to lifestyle change. Patients in the control group, the DSE group, did not gain weight. In fact, they slightly lost weight over time, so these patients weren’t out there doing nothing. They were actually doing a little bit and minding their health. Moreover, patients in both groups started out better in terms of their control than many of our patients. The average A1c level was 7.3% at the beginning of the trial. LDL cholesterol was 112 mg/dL, they had reasonable blood pressures, and their BMI was about 35. These were not terribly out-of-control patients. Some were, but on average they were a pretty well-controlled group going into this study.

We do know that weight loss and exercise can prevent diabetes. I am a big advocate of prevention, both early prevention of obesity altogether, as well as prevention of diabetes in individuals who have become overweight. Lifestyle changes can help prevent diabetes. Once you have diabetes, I think weight loss and exercise can have benefits, but they are not going to reduce the risk for the primary outcome that we set for Look AHEAD, which was a risk for macrovascular events or death. I think it is important to help put this trial into perspective for patients. Look AHEAD will now change into a cohort study in which we follow patients over time. There will be a lot more data coming from Look AHEAD that can be interpreted in the future.

This has been Dr. Anne Peters for Medscape. Thank you.

From Medscape.com

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