June 24th, 2013
Large NIH Trial Finds No Cardiovascular Benefits for Weight Loss and Exercise in Type 2 Diabetics
A large NIH-sponsored trial has found that an intensive lifestyle intervention was no better than standard care in reducing cardiovascular events in people with type 2 diabetes. The results of the Look AHEAD trial were presented today at the American Diabetes Association meeting and published simultaneously in the New England Journal of Medicine.
A total of 5,145 people with type 2 diabetes were randomized to either an intensive lifestyle intervention, focusing on weight loss through a low-calorie diet and increased exercise, or conventional diabetes care. Trial investigators had planned to run the study for as long as 13.5 years, in the hope of finding a significant difference in the rate of major cardiovascular events (death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for angina). However, after 9.6 years of followup the data and safety monitoring board performed an analysis and recommended that the trial be stopped for futility.
Major cardiovascular events occurred in 418 people in the control group versus 403 people in the intervention group (hazard ratio 0.95, CI 0.83-1.09, p=0.51). There were no significant differences in any of the individual components of the composite endpoint or any of the secondary outcomes. The results were consistent across the prespecified subgroups.
The trial did demonstrate the feasibility of long-term, modest weight reduction. People in the intervention group had lost 8.6% of their weight at 1 year, compared with 0.7% in the control group. At the end of the trial the difference had narrowed considerably, though there was still a statistically significant advantage for the intervention group (6% versus 3.5%). A similar pattern occurred with physical fitness, waist circumference, and glycated hemoglobin, with a large difference at 1 year in favor of the intervention group and a much smaller but still significant difference at the end of the trial. However, there were no significant differences at any time in LDL levels.
One ray of hope was that people in the intervention group were less likely to be treated with insulin during the first year of the trial and were more likely to have a partial remission of diabetes during the initial 4 years of the trial. In addition, as the trial investigators had previously reported, during the early years of the trial people in the intervention group had reductions in urinary incontinence, sleep apnea, and depression, and improvements in quality of life, physical functioning, and mobility.
The authors speculated that a larger weight loss in the intervention group might have produced better results, but observed that “the weight loss achieved in the intervention group is representative of the best that has been achieved with current lifestyle approaches.” They noted that the control group may have benefited from the increased use of statins, thereby lessening differences between the groups. They also speculated that the results might have been different with an alternative intervention, such as the Mediterranean diet.
In an accompanying editorial, Hertzel Gerstein takes an upbeat view of the trial, stating that physicians can tell their patients “that changes in activity and diet safely reduce weight, reduce the need for and cost of medications, reduce the rate of sleep apnea, improve well-being, and (in some cases) achieve a diabetes remission.” About the cardiovascular effects of intensive lifestyle interventions, physicians can “reassure their patients that intensive lifestyle interventions are unlikely to cause harm… and may provide a modest benefit. However,” he concludes, “even with no clear evidence of cardiovascular benefit, the Look AHEAD investigators have shown that attention to activity and diet can safely reduce the burden of diabetes and have reaffirmed the importance of lifestyle approaches as one of the foundations of modern diabetes care.”