An intensive lifestyle intervention that focused on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes mellitus (DM). However, the intervention led to many other benefits, including more weight loss over 10 years, clinically meaningful improvements in glycated hemoglobin levels, and less kidney disease and retinopathy.
The primary analysis of the randomized, controlled Look AHEAD trial revealed no significant differences in a composite of cardiovascular end points between those who had the intervention and those who only received advice. In 16 study centers in the United States, the Look AHEAD Research Group randomly assigned more than 5000 overweight or obese patients with type 2 DM to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive DM support and education (control group). Both groups continued to receive all of their medical care from their own health care provider.
The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
“There are several possible explanations for the lack of difference in cardiovascular events in the lifestyle arm compared to the comparison arm,” Rena Wing, PhD, Professor of Psychiatry and Human Behavior at Brown University in Providence, told ConsultantLive.
“One possibility is that it may have been difficult to see the benefits of weight loss in comparison to a control group that was provided education about nutrition and activity and in the context of pharmacologic therapy for diabetes and cardiovascular risk factors that was provided to both groups by their own physicians,” Dr Wing said. Another reason is that participants in the control group were receiving more medications, particularly statins, which could have lowered their risk of cardiovascular disease, she noted.
The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study. At 1 year, patients in the intervention group had lost an average of 8.6% of their initial body weight compared with 0.7% in the control group. At study end, the intervention group had a 6% weight loss compared with 3.5% in the control group. The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group.
The researchers did note other benefits for the intervention patients. “We have reported that the intensive lifestyle intervention led to improvements in sleep apnea, depression, urinary incontinence, and physical function and mobility,” said Dr Wing. “The lifestyle intervention also improved glycemic control and reduced the need for insulin.”
She added: “There are many reasons to lose weight and keep it off. Although this study did not show benefits for heart disease, it has shown that weight loss improves many other health problems. That’s an important message for primary care physicians to tell their patients with diabetes.”
The researchers reported their results in the June 24, 2013, New England Journal of Medicine.
The Wall Street Journal, “Lifestyle Intervention Did Not Reduce Cardiovascular Events in Obese Adults With Type 2 Diabetes”
Harvard Health Blog, “New trial muddies the water about diet, exercise, and diabetes”