June 24th, 2013

Large NIH Trial Finds No Cardiovascular Benefits for Weight Loss and Exercise in Type 2 Diabetics

A large NIH-sponsored trial has found that an intensive lifestyle intervention was no better than standard care in reducing cardiovascular events in people with type 2 diabetes. The results of the Look AHEAD trial were presented today at the American Diabetes Association meeting and published simultaneously in the New England Journal of Medicine.

A total of 5,145 people with type 2 diabetes were randomized to either an intensive lifestyle intervention, focusing on weight loss through a low-calorie diet and increased exercise, or conventional diabetes care. Trial investigators had planned to run the study for as long as 13.5 years, in the hope of finding a significant difference in the rate of major cardiovascular events (death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for angina). However, after 9.6 years of followup the data and safety monitoring board performed an analysis and recommended that the trial be stopped for futility.

Major cardiovascular events occurred in 418 people in the control group versus 403 people in the intervention group (hazard ratio 0.95, CI 0.83-1.09, p=0.51). There were no significant differences in any of the individual components of the composite endpoint or any of the secondary outcomes. The results were consistent across the prespecified subgroups.

The trial did demonstrate the feasibility of long-term, modest weight reduction. People in the intervention group had lost 8.6% of their weight at 1 year, compared with 0.7% in the control group. At the end of the trial the difference had narrowed considerably, though there was still a statistically significant advantage for the intervention group (6% versus 3.5%). A similar pattern occurred with physical fitness, waist circumference, and glycated hemoglobin, with a large difference at 1 year in favor of the intervention group and a much smaller but still significant difference at the end of the trial. However, there were no significant differences at any time in LDL levels.

One ray of hope was that people in the intervention group were less likely to be treated with insulin during the first year of the trial and were more likely to have a partial remission of diabetes during the initial 4 years of the trial. In addition, as the trial investigators had previously reported, during the early years of the trial people in the intervention group had reductions in urinary incontinence, sleep apnea, and depression, and improvements in quality of life, physical functioning, and mobility.

The authors speculated that a larger weight loss in the intervention group might have produced better results, but observed that “the weight loss achieved in the intervention group is representative of the best that has been achieved with current lifestyle approaches.” They noted that the control group may have benefited from the increased use of statins, thereby lessening differences between the groups. They also speculated that the results might have been different with an alternative intervention, such as the Mediterranean diet.

In an accompanying editorial, Hertzel Gerstein takes an upbeat view of the trial, stating that physicians can tell their patients “that changes in activity and diet safely reduce weight, reduce the need for and cost of medications, reduce the rate of sleep apnea, improve well-being, and (in some cases) achieve a diabetes remission.” About the cardiovascular effects of intensive lifestyle interventions, physicians can “reassure their patients that intensive lifestyle interventions are unlikely to cause harm… and may provide a modest benefit. However,” he concludes, “even with no clear evidence of cardiovascular benefit, the Look AHEAD investigators have shown that attention to activity and diet can safely reduce the burden of diabetes and have reaffirmed the importance of lifestyle approaches as one of the foundations of modern diabetes care.”






8 Responses to “Large NIH Trial Finds No Cardiovascular Benefits for Weight Loss and Exercise in Type 2 Diabetics”

  1. Enrique Guadiana, Cardiology says:

    The conclusions of the study are misleading since the patients in Intensive lifestyle intervention only achieve the aim weight loss in the first year and couldn’t maintain it. The Authors didn’t evaluate adhesion and they don’t mention how many reached the goals of diet and physical activity. They evaluate changes in physical fitness with a sub maximal stress test, this approach has many inconveniences and they only follow it in the year 1 and 4. Also I have to mention that a placebo was not given to participants in the control group, so participants were aware of their group assignment, introducing the possibility of a placebo effect. Not to mention the possibility the study lacked of sufficient power.

    The lack of significant difference in the rates of cardiovascular events could be explained if the patients had problems with adhesion and/or couldn’t achieve the recommended goals of diet and the fact that they are better than the control is not sufficient evidence that they achieved the goals.

  2. Marc Weisman, DO says:

    I hope Dr. Guadiana is correct because this flies in the face of conventional wisdom, common sense and our teaching of the past twenty years. It will also serve to disempower patients-the last thing we want to encourage.

  3. H Robert Silverstein, MD says:

    “Naïve data gathering” is the phrase my brilliant friend J T Guy, MD, taught me. Exactly!! When dealing with diabetes, “modest weight reduction” is hardly sufficient to benefit diabetics. The authors deserve serious criticism for such a minimalist approach to such a major problem. H Robert Silverstein, MD, FACC http://www.thepmc.org

  4. Martha Dickens, MD says:

    I help pts lose weight and comorbidities with a VLCD (very low calorie diet) which includes an exercise program. Many regain the weight and return in ~2 yrs to lose again. The baseline lab work on the second time around is almost always better than the initial diet’s baseline. This shows continued improvement in FBS, lipids and also the BP (or the number of antihypentive Rxs pts’ are on). This is after total weight regain and quitting exercise. This is a ‘legacy’ effect. Something just doesn’t add up on this Look AHEAD trial.

  5. Louis Krut, MB.ChB. MD says:

    Whenever we get results we do not care for someone finds a way to make that failure irrelevant or even appear to be a success. In this case Hertzel did a good job of the latter. If one bothers to make measures one must accept the facts, or not bother to look. It is all about the data, the rest is verbiage. One has to be tough to face data. Huxley put it rather well. Something like: “The great tragedy of science: The slaying of a beautiful hypothesis by an ugly fact.”
    But those who feel hurt need not despair. There will soon be another study giving you the results you know to be correct and then you can say you knew it all along.

  6. Karen Politis, MD says:

    Ouch! At first glance, a slap in the face of lifestyle modifications.
    But look at the things that did improve: diminished probability for insulin treatment (messing with syringes and needles, danger for hypoglycaemia), partial remission of diabetes (which I believe has been proven to decrease the horrible long-term complications like kidney disease, blindness, amputations etc.), and reduction in incontinence (I’ll take that!), sleep apnoea and depression.
    Sounds like a pretty good deal, considering you also look better, feel better and meet nice people as you walk, jog or dance.
    Avoiding “major” cardiovascular events is not the only purpose of lifestyle changes. They should improve your quality of life, which often consists of “minor” details. We should keep supporting our patients in taking better care of themselves.

  7. Anil Virmani, MD, DRM says:

    The trial results are more like “jumping to conclusions”. Neither the right comparison (The control group was on statins), nor the sufficient duration of the trial to achieve significant differences in cardiovascular effects, has skewed the results. But, there are a lot of other benefits. We should continue to advise our patients for the right life style changes and reduction in weight.

  8. Adrienn Kis, PhD says:

    Loosing weight for overweight and obese people is always good, but nearly 10 years follow-up is a long time, if they had diabetes they were not very young at the beginning, even if they benefited from losing or not gaining weight, they lost some of the benefit from advanced aging