Over the past few years I have been discussing the early successes of the Look AHEAD clinical trial, the largest lifestyle intervention study in Type 2 diabetic subjects, to date. The trial was a comparison of intensive lifestyle changes (calorie-restriction, physical activity and frequent group sessions) compared to standard diabetes counseling for weight management- with the primary outcome being changes in “hard” cardiovascular outcomes (MI, stroke, angina, cardiac death). Last month, the Look AHEAD trial was stopped due what was deemed “futility.” Researchers claim that since these hard primary end-points were no better (statistically) in the lifestyle group than the standard care group, they could call the trial a failure….it simply didn’t work, they claim.
Nothing could be further from the truth. As we have outlined on numerous occasions, the benefits of nearly every outcome measured has been statistically (and often overwhelmingly) favorable to the lifestyle intervention group. This includes dramatic weight loss at 1 year and even at 4 years, triglyceride reduction, HDL-cholesterol increases, reduced need for insulin and oral hypoglycemic drugs, increased fitness and mobility, reduced blood pressure, reductions in sleep apnea, reduced inflammatory biomarkers, and improved quality of life! However, these just happened not to be the primary end-points of the trial- so nothing to see here folks. [NIH Press Release]
Amazingly, they state “The intervention group did not have fewer cardiovascular events than the group receiving general diabetes support and education, but one positive factor we saw was that both groups had a low number of cardiovascular events compared to previous studies of people with diabetes,”[Emphasis added]. This tells us two things- since fewer events occurred in all participants [the details are explained here], the statistical power to detect a benefit for lifestyle changes was diminished- perhaps accounting for the apparent “futility”; but more importantly, stopping the trial may actually increase risk in both groups! There was certainly no harm in letting the trial continue for the next 2.5 years, since the safety committee readily admitted that there was no additional risk detected and nearly all secondary benefits were favoring the lifestyle intervention already. If both groups were receiving apparent benefits compared to previous diabetes trials, the “Do No Harm” approach would have been to keep the trial in place to understand why this was (likely requiring sub-group analysis).
This whole exercise just confirms the importance to both clinician and patient alike, of understanding how clinical trials are performed and how their data is interpreted. The whole 4th chapter of The Original Prescription is dedicated to this subject and I think it is absolutely critical if one is to fully understand how to make medical (or lifestyle) decisions based on published research. The months and years ahead will be full of data analysis, sub-group analysis and a wide variety of interpretations of this study data. Follow up data on these patients will be published for at least the next decade. From the data already collected, I predict we will see a vindication of the lifestyle intervention model, learning in due time why the primary outcome was not met before the trial was stopped. I will keep you posted. Meanwhile, peruse just a few of the recent abstracts of the benefits already published from the Look AHEAD trial below.
• Effect of improved fitness beyond weight loss on cardiovascular risk factors in individuals with type 2 diabetes in the Look AHEAD study.
• Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study
• Lifestyle change and mobility in obese adults with type 2 diabetes.
• Patterns of Weight Change Associated With Long-Term Weight Change and Cardiovascular Disease Risk Factors in the Look AHEAD Study.
• Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial.
• One-year changes in symptoms of depression and weight in overweight/obese individuals with type 2 diabetes in the Look AHEAD study.
• Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial.
• Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in type 2 diabetes: findings from the look AHEAD study.
• Body image changes associated with participation in an intensive lifestyle weight loss intervention.
• Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial.
• A 1-year lifestyle intervention for weight loss in individuals with type 2 diabetes reduces high C-reactive protein levels and identifies metabolic predictors of change: from the Look AHEAD (Action for Health in Diabetes) study.
I could go on- but we will stop there for now.