“The Look AHEAD trial showed no benefit in glucose control." "The Look AHEAD study didn't demonstrate a delay in progression of disease in type 2 diabetes." I heard these two statements while attending the Joslin Diabetes Innovation 2013 in Washington DC, October 3-5. One statement was made by a healthcare provider, the other by a marketing person who does outreach with physicians.
They echo the doom and gloom statements summarizing the Look AHEAD study that simply baffle me. But then I remember that the New England Journal of Medicine, in their social media push to publicize the first publication about Look AHEAD (June 27, 2013) since the study was halted about two years early in October 2012, offered up this negative conclusion. This Debbie downer headline then reveberated and snowballed through social media venues for the next 24 hours.
Too bad because at the same time the NEJM paper was being released, I had a front row seat at the American Diabetes Association in June 2013 when a handful of the study's lead principle investigators told a packed crowd in a huge lecture hall about their conjectures as to why the trial didn’t reduce heart attacks and stokes (and it wasn't all bad news). These experts also revealed a long list of positive outcomes about the trial.
I'll share what I heard and hope to read more about as more papers are published over the next few years.
The key research question in Look AHEAD was: Can an intensive lifestyle intervention (ILI) program which achieves and maintains weight loss [overtime] help prevent/delay the cardiovascular events which are the most common complication of type 2 diabetes?
Before jumping in it’s important to note that the Look AHEAD trial, which was planned for 13.5 years of follow up and was stopped after 11.5 years, will continue as an observational trial. Read my recap right after the trial was halted October, 2012.
To date one year data were published in Diabetes Care (June 2007) and four year data were published in the Archives of Internal Medicine (September 2010). I’ve recapped the four year findings here.
As you review these results and ongoing publications from the trial keep in mind the researchers achieved a study population retention rate of 96%. That’s huge!
One question on people’s minds at the ADA symposium was why the study was stopped a couple years early. Answer: the overseeing body for this NIH-conducted multicenter trial did what’s known as a “futility analysis” which showed that further study of the two groups would not elucidate any additional results.
As to the why there weren’t significant differences in CV events in the two groups, the investigators noted that larger weight loss may have been needed and perhaps the study was not long enough (Hmm but it was stopped early?). The presenters noted that the people in the control group (Diabetes Support and Education – DSE), experienced a greater use of statins (a drug category used to lower LDL) and possibly more intensive medical management of their CVD risk factors which might have closed a potential gap. (Note: the medical management of study subjects was done by their own health care providers). Keep in mind people in the DSE group likely received more diabetes support and education than the average person with type 2. So as a group the DSE subjects might have done better than a group of people with type 2 receiving "usual" usual care in the real world making it more difficult for the study to demonstrate a difference.
Researchers remarked, that even earlier intervention may be needed. Subjects in the trial had been diagnosed with type 2 6.8 + 6.5 yrs with a range of 3 months to 13 years. (Personally I hope there can and will be an analysis of the data based on subject’s years with diabetes.)
To the positive results:
- Weight loss. The ILI group lost their maximal weight (8.6%) by 1 year and had some weight regain, which is exactly what we’ve seen in many long term weight loss trials. This weight gain flattened out by the end of the study with a small amount of further weight loss. It was conjectured that this additional weight loss could be attributed to aging. They’ll be looking at whether this weight loss was more fat mass or lean body mass.
- Fitness: ILI had greater improvements.
- A1c: The greatest lowering of A1c was at one year, but the ILI group still maintained a significantly lower A1c at the study completion with less use of insulin compared to DSE. And again there appears to be some what's referred to as metabolic memory...the body remembers the earlier period of good control.
- Systolic BP: Greater improvement in ILI, but not in diastolic BP. The ILI group was less likely to use anti-hypertensive medication.
- Lipids: HDL- cholesterol more increased more in ILI group. LDL-cholesterol decreased in both groups but the ILI group required less statin medication.
- Chronic renal/kidney disease: 31% reduction in the ILI group.
- Retinopathy: Reduced self-reported symptoms in ILI group.
- Other health related improvements (in the ILI group): Less depression, sleep apnea and urinary incontinence.
And to the question, did people in the ILI group save on health care resources? The answer from Henry Glick, PhD, a health economist with the trial showed data that the ILI group had reduced cumulative hospitalizations, used less medications (insulin, anti-hypertensives, statins) and generally utilized less health care services.
In my mind, the results of the Look AHEAD trial should hardly be headlined as doom and gloom. They add up to quite a laundry list of positive health benefits for people with type 2 diabetes trying to get and stay healthy over the years. And cost savings for our healthcare system, too.
(Parts of this blog were initially published on diabetesmine.com July 2013.)