The intensive lifestyle intervention used in type 2 diabetes patients in the Look AHEAD trial was deemed futile over time.
Frank J. Domino, MD
Wing RR, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes: Look AHEAD trial. N Engl J Med. 2013 Jul 11;369(2):145-54. http://www.nejm.org/doi/full/10.1056/NEJMoa1212914.
This was a randomized controlled trial of more than 5,000 overweight or obese patients with type 2 diabetes.
The study population was aged between 45 and 75 years old and had type 2 diabetes. Patients who took insulin had a body mass index (BMI) of 27.0 or greater, while patients who weren’t taking insulin had a BMI of 25.0 or greater.
All of the patients had a glycated hemoglobin level of at least 11%, a systolic blood pressure below 160 mm Hg, a diastolic blood pressure below 100 mm Hg, a triglyceride level below 600 mg/dl (6.77 mmol/l), an established relationship with a primary care provider, and the ability to complete a valid maximal exercise test. Patients could have used any type of glucose-lowering medication, but the trial limited insulin use to less than 30% of the patient population.
Intervention and Control
Patients were randomized to either an intensive lifestyle intervention group that “promoted weight loss through decreased caloric intake and increased physical activity” or a control group that received diabetes education and support. The intervention group was counseled on lifestyle changes according to the following schedule:
With an expressed goal of achieving and maintaining weight loss of at least 7%, interventions of the intensive intervention program included a caloric intake goal of 1,200 to 1,800 kcal per day — with less than 30% of calories from fat and less than 15% from protein — as well as at least 175 minutes of moderate-intensity physical activity per week.
Within the control group, there were 3 annual group sessions that focused on diet, exercise, and social support throughout years 1 through 4; thereafter, the counseling frequency was reduced to 1 session annually.
Results and Outcomes
There was more weight loss in the intensive lifestyle intervention group than in the control group (8.6% versus 0.7% at year 1; 6.0% versus 3.5% at year 4), Additionally, the intervention group had greater improvements in fitness and all cardiovascular (CV) risk factors — with the exception of low-density lipoprotein (LDL) cholesterol — while reductions were seen in hemoglobin A1C levels, female sexual dysfunction, urinary incontinence, sleep apnea, and depression. The intervention group also recorded improvements in quality of life, physical functioning, and mobility.
The study’s primary outcome was a composite of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during the follow-up period. Secondary outcomes included 3 composite CV results: Death from CV causes, nonfatal myocardial infarction, or nonfatal stroke; death from any cause, myocardial infarction, stroke, or hospitalization for angina; and death from any cause, myocardial infarction, stroke, hospitalization for angina, hospitalization for heart failure, coronary-artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or peripheral vascular disease.
The primary outcome occurred in 403 patients within the intervention group (1.83 events per 100 person-years) and 418 patients within the control group (1.92 events per 100 person-years; 95% confidence interval [CI], 0.83 to 1.09; P = 0.51). The trial was stopped early on the basis of a futility analysis with a median follow-up of 9.6 years.
Despite significant reductions in weight and CV risk factors after 1 year of intensive lifestyle intervention, the composite endpoints of the primary outcome didn’t differ between the intervention group and the control group just before the 10-year mark, and the study was stopped. Based on the study’s protocol, no CV benefit was recorded in the intervention group compared to the control group.
This study’s initial intervention of weekly lifestyle counseling for high-risk patients led to significant reductions in intermediate end points — including weight and glycohemoglobin — as well as improvements in fitness and quality of life. With the possible exception of gastric bypass, there aren’t any medical interventions that would produce this combination of improvements within a year.
However, the study was deemed futile over time as the intensive nature of the intervention was reduced. At an approximate 10-year mark, no benefit was seen on the combined endpoint of death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina.
Though the study authors concluded that the interventions didn’t improve outcomes, they should consider examining the potential benefit of continuing the first 6 months of their intervention schedule — especially since many commercial weight loss programs recommend weekly in-person contact and counseling. The authors could also study a more aggressive weight loss goal, as this study’s goal was an extremely modest 7% weight loss over 13 years; for a 300-pound patient, that translates to a weight loss of 21 lbs.
Further research on the effects of intensive lifestyle interventions should be far more intensive than the majority of this study’s intervention. Future researchers should provide long-term weekly counseling on diet and exercise, use a higher protein dietary recommendation, plan for more substantial weight loss over time, and continue to follow all endpoints. With this prolonged intervention, there’s a greater chance of achieving an improved CV risk.
This study’s conclusions must influence your care. Intensive lifestyle changes are critical for improving outcomes in obesity and type 2 diabetes, as the American Diabetes Association (ADA) recommends intensive medication-based interventions for only those patients who exercise and follow a healthy diet.1 Let’s just hope the next study of an intensive intervention will be truly intensive and result in lower rates of morbidity and mortality.
1. Skylar JS, et al. Intensive glycemic control and the prevention of cardiovascular events: Implications of the ACCORD, ADVANCE, and VA Diabetes trials. Diabetes Care. 2009; 32(1): 187-192. http://care.diabetesjournals.org/content/32/1/187.full.
About the Author
Frank J. Domino, MD, is Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School in Worcester, MA. Domino is Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins). Additionally, he is Co-Author and Editor of the Epocrates LAB database, and author and editor to the MedPearls smartphone app. He presents nationally for the American Academy of Family Medicine and serves as the Family Physician Representative to the Harvard Medical School’s Continuing Education Committee.