October 24, 2012

Let’s Look Ahead From Look AHEAD

Have you heard that the Look AHEAD (Action for Health in Diabetes) randomized controlled trial conducted through National Institutes of Health (NIH) was ended two years ahead of schedule? This news crossed my eyes first on 10/20/2012 via twitter. Got to love twitter!

The press information from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), announced on 10/19/2012 that the trial had been stopped about a month earlier – in September. Why? Because in this long and lengthy trial, in which people had been enrolled for up to 11 years, the people in the intensive lifestyle intervention (ILI) group did not experience a decrease in cardiovascular events (CV) (heart attacks, strokes, etc.) compared with the people in the control group. 

The Key Look AHEAD Question…and Answer
Can an intensive lifestyle intervention program (ILI) which achieves and maintains weight loss help prevent/delay the heart and circulatory problems which are the most common complications of type 2? 

It appears that the long term answer is no, however, (and this is a BIG however), it’s worth noting that the rate of CV events in both the control and ILI group were lower than expected in the first 5 years of the trial. It may well be that all study subjects (both ILI and the control group who received more attention than many people with type 2 in our population) received better overall diabetes care, lifestyle education and support.   

The Look AHEAD researchers have been given the go ahead to continue to follow people who were in the ILI group to determine if they experience any reduction in CV events in the ensuing years. 

Look AHEAD Results to Date
Plenty of data has been collected on this study population and some has been published during the course of the long, arduous study. The one year results were published in Diabetes Care: June, 2007. The key finding from the first year was that people who were in the ILI group and received a significant amount of support lost significantly more weight than people in the control group. Four year data was published in the Archives of Internal Medicine, Sept 27, 2010. These data followed the same weight loss pattern we’ve seen repeatedly in weight loss studies – maximal weight loss by six months to one year and then a slow weight regain back towards starting weight – but not complete weight regain. Eight year data is forthcoming. The blog Look At What the Look AHEAD Study Reveals offers more details of the study and results.  

Beyond the Headlines
As is usual with the media the Look AHEAD trial has been summarized simplistically. This includes the New York Times coverage which stated in the first sentence, [the study]…”has ended two years ahead of schedule because the intensive program did not help.” In looking at this data and our learnings it’s important to note that study subjects had type 2 diabetes for an average duration of 7 years at the start of the study (with a wide expanse of duration from 3 months to 13 years) which means after up to 11 years of the study they had had type 2 an average of 18 years. 

And the important take aways... 

  1. Type 2 diabetes is a progressive disease: The Look AHEAD results reinforces a key point we’ve been learning about type 2 diabetes over the last couple of decades (since the United Kingdom Prospective Diabetes Study (UKPDS) – it’s a progressive disease in which people make a dwindling supply of insulin. We now know that even at diagnosis peoples’ insulin supply/function is quite diminished. 
  2. Type 2 requires early, aggressive treatment: We’ve been learning, and Look AHEAD reinforces, that Type 2 diabetes requires immediate and serious attention at diagnosis. Better yet, we should be doing a much better job helping people diagnose prediabetes when people can get an even greater head start on a healthier lifestyle and prevent or slow they’re onset of type 2. (I’m hoping the Look AHEAD data can be mined to determine if people who were enrolled in the study early on in their type 2 diagnosis faced improved odds of reducing cardiovascular disease?)  
  3. People with type 2 diabetes can lose weight: Indeed Look AHEAD showed that with sufficient ongoing support (yes, a significant amount of support from expert facilitators delivered at no expense to the subjects!) people can lose weight and keep a sufficient amount of that weight off. We’ve learned key lessons to help people achieve this goal. For starters: intensive help and support early on matters, meal replacements can help some people control minimize food decisions and calorie intake, and exercise (and lots of it) plays a key role in success. 
  4. Weight loss and a healthier lifestyle can improve health over the years: People in the ILI group during the course of the study experienced improvements in their health parameters. People lowered their blood glucose levels, more often achieved improved A1cs, lowered blood pressure and were able to normalize their lipids more often. And these improvements occurred for some people on fewer medications (including glucose lowering, blood pressure and lipid medications) than the people in the control group. 
  5. Healthy lifestyle (that’s weight loss, healthy eating and physical activity) must be partnered with glucose lowering medications as needed to control blood glucose: To say the least medications available to manage glucose and insulin resistance - a key problem in type 2 diabetes - have come a long way in the last nearly 20 years. I fear this is not common knowledge among consumers.) With these new medications available it’s critical that we help consumers change their thinking about them. People often think if they have to take a glucose lowering medication, they’re a failure or they have “bad” diabetes. Reality is research shows it’s critical that, once diagnosed with diabetes, most people need to partner a healthy lifestyle with one or more glucose lower medication. (In addition, it’s critical for people to control their blood pressure and blood lipids. In this case as well, lifestyle changes should be paired with medications.)

As more data from Look AHEAD becomes available, more conclusions will be revealed. For the moment, as David Nathan, MD, Director of the Diabetes Center at Massachusetts General Hospital and a Look AHEAD principal investigator aptly put these Look AHEAD results in context in the New York Times article, “We showed that meaningful weight loss could be established and maintained…The group assigned to diet and exercise [ILI] ended up with about the same levels of cholesterol, blood pressure and blood sugar as those in the control group, but the dieters used fewer medications...That may be the choice we are highlighting…You can take more medications…or you can chose a lifestyle intervention and use fewer drugs and come to the same cardiovascular disease risk.”    

In my eyes, the Look AHEAD study was hardly a “diet and exercise” failure!