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Subanalyses of Look AHEAD Trial Upset Some Conventional Wisdom
The Look AHEAD Trial is a prospective, randomized controlled trial (RCT) involving approximately 5000 individuals with type 2 diabetes (T2D). Four-year subanalyses from this 13.5-year trial were presented in a symposium held at the American Diabetes Association 71st Annual Scientific Sessions in San Diego, California on Friday, June 23, 2011. The goal of LookAHEAD is to compare outcomes from intensive lifestyle intervention (ILI) versus diabetes support and education (DSE).
Contrary to conventional wisdom which holds that lifestyle interventions in the severely obese are unavailing, ILI was somewhat more effective for severely obese (body mass index [BMI] ≥ 40 kg/m2) patients with T2D than for those who are merely overweight. Severely obese patients lost slightly more weight in both arms of the trial than other study participants. A total of 38% of severely obese patients attained weight loss ≥ 10% in the first year of the trial, compared to 30% of overweight patients. At 4 years, 47% of the severely obese patients maintained weight loss ≥ 10%, whereas 38% of overweight patients did the same.
Conventional wisdom also holds that ILI cannot reverse T2D. The Look AHEAD trial found that disease regression (A1C ≤ 6.5% without medications) was indeed uncommon, but that once achieved, about 67% remained in remission for 4 years. Factors predicting success included baseline A1C < 7.5% and diabetes duration < 5 years. Patients with baseline cardiovascular disease and those using ≥ 3 antidiabetic medications were less likely to attain regression.
The Sleep AHEAD substudy (n = 305) is the only long-term RCT of weight loss on obstructive sleep apnea. While the prevalence of sleep apnea in the general population is approximately 4% for women and 9% for men, in Sleep AHEAD the crude prevalence was 87%; after adjusting for various confounders, including a history of sleep apnea, the prevalence was 88%. Patients treated with ILI had a decrease in sleep apnea severity at 1 year that continued for 4 years; patients treated with DSE had an increase in sleep apnea severity at 1 year that remained stable for 4 years. Sleep AHEAD showed that ILI affected sleep apnea severity independently from weight loss.
Conventional wisdom says that patients on insulin therapy have a harder time losing weight than patients on other antidiabetic medications. Look AHEAD found that there was no significant difference in weight loss in the ILI arm between insulin users and nonusers. Regardless of antidiabetic regimen, weight gain was more likely with DSE (55% of patients in this arm) and less likely with ILI (26% of patients). The strongest predictor of sustained weight loss at 4 years was the amount of weight lost at the end of the first year, which explained 21.9% of the variance in outcomes. The odds ratios for maintaining weight loss by 1-year weight loss strata relative to weight loss < 5% were 2.0 (95% confidence interval [CI] 1.41-2.96) for 5-9.99% loss and 9.8 (95% CI 6.99, 13.74) for ≥ 10%. Interestingly, and again contrary to conventional wisdom, the oldest patient group (65-76 years) had better weight loss and adherence to therapy than younger age groups.
Look AHEAD shows that ILI is more effective than DSE for many different outcomes over 4 years. At 4 years, the number of patients dropping out of the study has been enviably low, with > 93% retention. Cardiovascular outcomes data is being collected and will be reported after the study is unblinded.
Further Reading:
Look AHEAD baseline data are reported in Pi-Sunyer X, et al. Diabetes Care. 2007;30:1374-1383.
Look AHEAD 4-year outcomes are reported in Look AHEAD Research Group, Wing RR. Ann Intern Med. 2010;170:1566-1575.
Sleep AHEAD outcomes are reported in Foster GD, et al. Diabetes Care. 2009;32:1017-1019.