Looking Back at Look AHEAD
Last week, the US National Institutes of Health (NIH) announced the discontinuation of the intensive diet and lifestyle interventions in the Look AHEAD (Action for Health in Diabetes) study.
This study, now in its eleventh year, was designed to compare the effects of an intensive diet and lifestyle program designed to promote and sustain weight loss versus ‘usual care’ on the prevention of heart attacks, strokes and cardiovascular deaths in individuals with long-standing type 2 diabetes.
The study was conducted at 16 centers across the United States included 5,145 people who were 45 to 76 years old when they enrolled in the study. Sixty percent of participants were women.
Participants in the intervention group lost more than 8% of their initial body weight after one year of intervention and maintained an average weight loss of nearly 5 percent at four years.
This reduction in body weight was accompanied by significant improvements in glycemic control and numerous other health benefits (e.g. decreased sleep apnea, improved mobility and quality of life).
However, given a remarkably low incidence of ‘hard’ endpoints in both the interventions and control groups, it became evident the the study would stand little chance of demonstrating superiority of the lifestyle intervention in terms of preventing cardiovascular complications.
These results are perhaps not all that surprising, given that recent pharmacological studies in patients with type 2 diabetes have also failed to show a significant reduction in cardiovascular deaths.
Moreover, readers may be aware that even with the substantially greater reduction in body weigh with bariatric surgery, the Swedish Obesity Surgery study, took over 13 years to demonstrate a barely significant reduction in myocardial infarcts (but not deaths!) in patients with type 2 diabetes.
In hindsight, hoping for a greater impact with diet and exercise than even that seen with bariatric surgery would seem rather optimistic (to be fair, the surgical data were not available at the time this study was planned).
Nevertheless, according to the recommendations of the Data Monitoring Board, the study should be continued (without the intervention) to determine the long-term outcomes in the participants.
While the results of this study are certainly disappointing to the researchers involved, they do provide important lessons for designing future trials of obesity treatments in patients with type 2 diabetes.
Not only may future studies have to enrol a substantially greater number of participants but such studies may also need to substantially enrich the study population with higher risk individuals to increase event rates (i.e. EOSS Stage 3 rather than just EOSS Stage 2 patients).
Obviously, the wild card here is whether or not ANY amount of weight loss will suffice to reduce mortality in a population that already has well-established heart disease (remember the obesity paradox).
Thus, whether or not weight loss (through lifestyle interventions or otherwise) will save lives in individuals with established type 2 diabetes may well, in the end, be a question, to which we will never quite know the answer.