On 2014 Mar 24, Valter Silva commented:

LOOKing AHEAD... without losing sight plausibility

The LOOK AHEAD,¹ a rigorous study and paradoxical, showed no reduction in the rates of cardiovascular events or mortality with lifestyle interventions in type 2 diabetic patients. Several hypotheses have been raised:² (1) cardioprotective medications in the intervention group; (2) reduced effect after the first year; (3) lifestyle interventions need more follow-up; (4) unreliable outcomes masked the effect. Furthermore, could diabetes support and education (control group) produce beneficial changes by empowering patients? Yes! It is perfectly plausible and supported by a large body of evidence that interventions such as the control group received produces benefits, masking lifestyle intervention possible benefits. Considering the principle of plausibility of evidence-based medicine, exemplified by a systematic review of randomized controlled trials³ about parachutes effectiveness for preventing death and major trauma, sometimes observational designs bring the best evidence. In brief, even with the findings of the LOOK AHEAD,¹ yet it is not plausible not to recommend interventions to change lifestyle, at the risk of stating that results of large studies (e.g. He J, 2005⁴ and Lee IM, 2012⁵ ) are not valid. In our viewpoint, instead of to declare "lifestyle intervention does not work", a plausibility conclusion for these results is "lifestyle intervention is quite as good as to receive diabetes support and education".

Valter Silva, PhD, Research assistant, Universidade Federal de São Paulo, SP, Brazil

Antonio Jose Grande, PhD, Associate professor, Universidade do Extremo Sul Catarinense, SC, Brazil

Competing interests: None declared.

Reference:

1. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-154.

2. Gerstein HC. Do lifestyle changes reduce serious outcomes in diabetes? N Engl J Med. 2013;369(2):189-90.

3. Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ 2003;327(7429):1459-61.

4. He J, Gu D, Wu X, et al. Major causes of death among men and women in China. N Engl J Med 2005;353(11):1124-34.

5. Lee IM, Shiroma EJ, Lobelo F, et al.; Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012;380(9838):219-29.

On 2013 Oct 20, Carl Heneghan commented:

Id agree with Naama Constantini comments in that intensive lifestyle interventions do not reduce CVD, based one trials findings alone. It shows the added precision of setting clinical trials in the light of systematic reviews. I believe the Lancet asks for this with all new trials, and it would be helpful for other journals to follow suit, when forming their conclusions.

On 2013 Sep 28, Mayer Brezis commented:

We question the authors’ conclusion that an intensive lifestyle intervention does not reduce cardiovascular events among overweight diabetic patients (1). As their results included a subgroup analysis for patients with cardiovascular disease at baseline, this interpretation seems to contradict consistent > 25% reductions in all-cause and cardiac mortality as well in cardiac morbidity from a systematic review of 23 trials on lifestyle modification in 11,085 randomized coronary heart disease patients (2). The paper reveals no information on the effect of the intervention on actual physical activity (pedometers were given to patients but data are not shown). Physical fitness was low, somewhat increased for a couple of years and then reverted to baseline, but is not reported for most of the ensuing years. Since adherence appears to have been low, a per-protocol analysis might have enriched our understanding beyond an intention-to-treat analysis. As for medications, poor adherence is common and deserves better accounting (3). We suggest rephrasing the conclusion to say that a limited lifestyle intervention focused on weight loss had little impact of cardiovascular events.

Naama Constantini, MD, DFM, FACSM, Dip. Sport Med. (CASM)<br> Mayer Brezis, MD, MPH Hadassah Hebrew University Medical Center Jerusalem, Israel Robert Sallis, MD Department of Family Medicine and Sports Medicine Kaiser Permanente Medical Center Fontana, CA, USA

(1) The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England Journal of Medicine 2013;369:145-54.

(2) Janssen V, Gucht VD, Dusseldorp E, Maes S. Lifestyle modification programmes for patients with coronary heart disease : a systematic review and meta-analysis of randomized controlled trials. European Journal of Preventive Cardiology 2013;20:620-40.

(3) Osterberg L, Blaschke T. Adherence to medication. New England Journal of Medicine 2005;353:487-97.

On 2013 Sep 28, Mayer Brezis commented:

We question the authors’ conclusion that an intensive lifestyle intervention does not reduce cardiovascular events among overweight diabetic patients (1). As their results included a subgroup analysis for patients with cardiovascular disease at baseline, this interpretation seems to contradict consistent > 25% reductions in all-cause and cardiac mortality as well in cardiac morbidity from a systematic review of 23 trials on lifestyle modification in 11,085 randomized coronary heart disease patients (2). The paper reveals no information on the effect of the intervention on actual physical activity (pedometers were given to patients but data are not shown). Physical fitness was low, somewhat increased for a couple of years and then reverted to baseline, but is not reported for most of the ensuing years. Since adherence appears to have been low, a per-protocol analysis might have enriched our understanding beyond an intention-to-treat analysis. As for medications, poor adherence is common and deserves better accounting (3). We suggest rephrasing the conclusion to say that a limited lifestyle intervention focused on weight loss had little impact of cardiovascular events.

Naama Constantini, MD, DFM, FACSM, Dip. Sport Med. (CASM)<br> Mayer Brezis, MD, MPH Hadassah Hebrew University Medical Center Jerusalem, Israel Robert Sallis, MD Department of Family Medicine and Sports Medicine Kaiser Permanente Medical Center Fontana, CA, USA

(1) The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England Journal of Medicine 2013;369:145-54.

(2) Janssen V, Gucht VD, Dusseldorp E, Maes S. Lifestyle modification programmes for patients with coronary heart disease : a systematic review and meta-analysis of randomized controlled trials. European Journal of Preventive Cardiology 2013;20:620-40.

(3) Osterberg L, Blaschke T. Adherence to medication. New England Journal of Medicine 2005;353:487-97.

On 2013 Oct 20, Carl Heneghan commented:

Id agree with Naama Constantini comments in that intensive lifestyle interventions do not reduce CVD, based one trials findings alone. It shows the added precision of setting clinical trials in the light of systematic reviews. I believe the Lancet asks for this with all new trials, and it would be helpful for other journals to follow suit, when forming their conclusions.

On 2014 Mar 24, Valter Silva commented:

LOOKing AHEAD... without losing sight plausibility

The LOOK AHEAD,¹ a rigorous study and paradoxical, showed no reduction in the rates of cardiovascular events or mortality with lifestyle interventions in type 2 diabetic patients. Several hypotheses have been raised:² (1) cardioprotective medications in the intervention group; (2) reduced effect after the first year; (3) lifestyle interventions need more follow-up; (4) unreliable outcomes masked the effect. Furthermore, could diabetes support and education (control group) produce beneficial changes by empowering patients? Yes! It is perfectly plausible and supported by a large body of evidence that interventions such as the control group received produces benefits, masking lifestyle intervention possible benefits. Considering the principle of plausibility of evidence-based medicine, exemplified by a systematic review of randomized controlled trials³ about parachutes effectiveness for preventing death and major trauma, sometimes observational designs bring the best evidence. In brief, even with the findings of the LOOK AHEAD,¹ yet it is not plausible not to recommend interventions to change lifestyle, at the risk of stating that results of large studies (e.g. He J, 2005⁴ and Lee IM, 2012⁵ ) are not valid. In our viewpoint, instead of to declare "lifestyle intervention does not work", a plausibility conclusion for these results is "lifestyle intervention is quite as good as to receive diabetes support and education".

Valter Silva, PhD, Research assistant, Universidade Federal de São Paulo, SP, Brazil

Antonio Jose Grande, PhD, Associate professor, Universidade do Extremo Sul Catarinense, SC, Brazil

Competing interests: None declared.

Reference:

1. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-154.

2. Gerstein HC. Do lifestyle changes reduce serious outcomes in diabetes? N Engl J Med. 2013;369(2):189-90.

3. Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ 2003;327(7429):1459-61.

4. He J, Gu D, Wu X, et al. Major causes of death among men and women in China. N Engl J Med 2005;353(11):1124-34.

5. Lee IM, Shiroma EJ, Lobelo F, et al.; Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012;380(9838):219-29.