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CHICAGO – A decade of diet and exercise had no effect on cardiovascular morbidity and mortality in overweight and obese adults with type 2 diabetes, according to a randomized, federally funded study that was stopped 2 years early due to futility.
"However, there are many reasons why, I would argue, that you should be encouraging patients with diabetes to lose weight," said Rena R. Wing, Ph.D., the trial’s chair. The results showed that the participants who were in the diet and exercise group, "are less likely to have kidney disease, have less incidence of depression, lower hospital costs, and less medication costs, so there are still many advantages to intense lifestyle interventions," Dr. Wing said during the presentation of the findings at the annual scientific sessions of the American Diabetes Association.
The results also showed that the participants were able to maintain a modest weight loss during a 10-year period.
The Look AHEAD (Action for Health in Diabetes) trial aimed to fill a gap in existing data about whether intensive lifestyle intervention would decrease cardiovascular morbidity and mortality of patients with type 2 diabetes in the long term.
Researchers recruited more than 5,100 patients and randomized them to the intensive lifestyle intervention program, which decreased calorie intake and increased exercise, or to the control group, which provided diabetes support and education. The goal of the intervention was achieving and maintaining weight loss of at least 7% through group and individual counseling.
The trial’s primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. The trial was planned to have a greater than 80% probability of detecting an 18% difference in cardiovascular events between the two arms, assuming that two-sided alpha was 0.05, a primary outcome rate of 2% per year in the control group, and the planned maximum follow-up of 13.5 years.
But in September 2012, the trial was stopped at the request of its primary sponsors, based on a futility analysis. The median follow-up at the time was 9.6 years.
By then, 403 patients in the intervention group and 418 patients in the control group had met the trial’s primary outcome, with no statistically significant difference between the two groups (1.83 and 1.92 events per 100 person-years, respectively).
Why didn’t it work?
Researchers listed several possible explanations for the results. The study may have had insufficient power, although that wouldn’t explain the negative results, the authors wrote. It is also possible that a higher sustained weight loss was needed in the intervention group to reduce the risk of cardiovascular disease. Meanwhile, the educational sessions and increased use of statins in the control group may have lessened the difference between the two groups, the authors noted. And intensified medical management of cardiovascular risk factors for both groups may have made the relative benefit of the intensive lifestyle intervention more difficult to demonstrate, they added.
Earlier intervention during the course of diabetes may be needed, they added. The results were published online simultaneously with the presentation (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMoa1212914]).
In an editorial accompanying the published results, Dr. Hertzel C. Gerstein wrote that the inclusion of "the somewhat unreliable outcome of hospitalization for angina in the primary composite outcome may have added noise and further obscured any emerging signal" (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMe1306987]).
During the presentation, an audience member suggested that since the 1-year and 4-year findings of the trial were published and well publicized, the participants in the control group might have taken it upon themselves to take action and lose weight. The panel of investigators said that is also a possibility.
Dr. Peter H. Bennett, who is one of the trial’s investigators and was cochair of eligibility, said that stopping the trial "was a big mistake," and that it should have been carried on at least until the planned termination point. "They stopped this trial because they were projecting that if they carried on for 2 more years, the differences in the primary endpoint were unlikely to be statistically significant. But there are several problems. First, you prejudice the power to analyze any other events, and just as we’ve learned from natural history of diabetes-related mortality, it’s clear that you don’t see excess diabetes-related mortality until they’ve had at least 15 years of diabetes, and that’s just at the point that the trial was stopped," Dr. Bennett, scientist emeritus at the National Institutes of Health – one of the main funders of the trial – said in an interview.
"It is also possible that lifestyle interventions may have a real but modest effect on cardiovascular outcomes akin to that of glucose lowering (e.g., a 10%-15% reduction) that requires more than 10 years to become apparent. If so, this trial was clearly too small to detect such an effect," wrote Dr. Gerstein, an endocrinologist and professor at McMaster University and Hamilton Health Sciences, Hamilton, Ont.
A look at the data
The patients in the intervention group (2,570) and control group (2,575) had similar characteristics at baseline. They were between 45 and 75 years old, were mostly female (60%) and white (63%), and had a mean body mass index of 36.0. Fourteen percent had a history of cardiovascular disease, and the median duration of diabetes was 5 years. Less than 30% were on insulin.
Close to 96% of the patients stayed in the trial.
During months 1 and 6, the intervention group had weekly contact with staff members. The contact was gradually reduced in the following months to one on-site individual session per month, and one phone call or e-mail per month from 2 years onward. The patients’ medications were adjusted by their own physicians.
Patients in the control group had 3-4 meetings per year during years 1 through 4, and after that, they had one meeting per year. They received education on diet, exercise, and social support.
Weight loss was greater in the intervention group compared with the control group, with the greatest difference at 1 year (8.6% vs. 0.7%), but it remained significant through the end of the study (6.0% vs. 3.5%).
Specifically, the intervention group had an initial weight loss of 8.6%, followed by weight regain in the first 5 years, and then gradual weight loss, leading to average weight loss of 6%. The control group had a gradual but consistent weight loss, for an average of 3.5% at the end of the trial.
One audience member suggested that some of the weight loss might have been due to aging. The authors said they are looking at those factors in their ongoing data analysis, which they’re planning to publish in the near future.
Meanwhile, the intervention group had significantly greater weight loss than did the control group throughout the trial. They had significantly greater improvements in fitness, hemoglobin A1c levels, systolic blood pressure, and HDL cholesterol (P less than .05 for all). The control group had significantly greater reductions in LDL cholesterol (P less than .05), although they also had a significantly greater use of medications, including insulin, statins, and antihypertensives, compared with the intervention group, the authors noted.
In the short-term (1-4 years), the intervention group saw improvements in cardiovascular risk factors, preservation of mobility, and improvements in fitness, obstructive sleep apnea, fatty liver disease, urinary incontinence, sexual function, and markers of inflammation.
The intervention also reduced the incidence of high-risk chronic kidney disease by 31%, and reduced the total costs and service utilization, especially related to hospitalization ($2,500 per participant), and medication ($2,500 per participant), the authors reported. Although the intervention didn’t affect neuropathy symptoms, it reduced the incidence of reported retinopathy by 14%, reduced the incidence of symptoms of mild or greater depression by 20%, and slowed age-related decline in reported physical function.
Program reduced burden of diabetes
"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 approach as one of the foundations of modern diabetes care," Dr. Gerstein wrote in his editorial, adding that the data show "intensive lifestyle interventions are unlikely to cause harm and may provide a modest benefit."
Interactions among subgroups – history of cardiovascular disease at baseline, and gender, race/ethnicity – showed nonsignificant interaction with cardiovascular disease history (P = .06).
Summarizing the study’s limitations, the authors said that it’s not clear whether changing the intervention groups’ dietary composition might have yielded different results. Their diet during the intervention was 1,200 to 1,800 kcal/day, with less than 30% of calories from fat, and less than 15% from protein. Authors added that the patients recruited successfully competed the fitness test at baseline, so the results can’t be generalized to all patients with type 2 diabetes.
Although the intervention has stopped, the trial continues as an observational study, said Dr. Wing. And some wonder if longer-term results would reveal new information.
"My prediction is that even after stopping the trial, as long as follow-up is carried on for several more years, you’ll see differences in total mortality," said Dr. Bennett, citing the results of UK Prospective Diabetes Study (UKPDS), which showed no difference in cardiovascular disease at 12 years, but a significant difference at 20 years. "So it does appear that intervention does have a lasting but delayed effect on that endpoint."
"I hope [the results] are not misinterpreted," Dr. Bennett continued. "There’s a danger given the lack of effect of the primary endpoint that the headlines will say weight loss is useless, and that’s a total misinterpretation in my view. There are multiple reasons to encourage weight loss. Other than the fact that it doesn’t appear to affect mortality up to this point, it seems to have benefit for all sorts of other things – people feel better, walk better, they develop advanced renal disease less frequently, their cholesterol and blood pressure are lower. I hope that message gets through rather than the negative one."
Dr. Wing, Dr. Bennett, and Dr. Gerstein had no disclosures relevant to the trial. The trial was supported by the National Institutes of Health, other Department of Health and Human Services agencies, and several companies including FedEx, Johnson & Johnson, Nestle Healthcare Nutrition, and Abbott Nutrition.
On Twitter @NaseemSMiller
I think the trial has a good message: that lifestyle can work, that intervention can work, that education can work, but it's not the only solution. For many people with diabetes, we must use medication. And, in many people with coronary disease, we must use medications. But to call it a failed trial is ridiculous, in my mind. If I can delay complications by 4 or 5 years, then we did well, we saved money, and we improved somebody's life.
We saw a 6% reduction in weight over 10 years. This is awesome and has never been shown before. Actually 3.5% reduction in weight [over 10 years] hasn't been shown before. I think that if you read the study, a lot of good stuff came out of it.
I will tell my patients how well the lifestyle management works. But I still will tell them that lifestyle is important, but many times, it needs to come in combination with medication.
My issue is that the trial was cut [short]. They saw that other aspects improved, and they should have continued to see what it means. It's like anything; we want fast solution to long-term tissues. Maybe we need to see a population study over 25 or 30 years.
Dr. Yehuda Handelsman is the medical director and principal investigator of Metabolic Institute of America, and president-elect of the American College of Endocrinology. He is on the advisory board for Clinical Endocrinology News.
I think the trial has a good message: that lifestyle can work, that intervention can work, that education can work, but it's not the only solution. For many people with diabetes, we must use medication. And, in many people with coronary disease, we must use medications. But to call it a failed trial is ridiculous, in my mind. If I can delay complications by 4 or 5 years, then we did well, we saved money, and we improved somebody's life.
We saw a 6% reduction in weight over 10 years. This is awesome and has never been shown before. Actually 3.5% reduction in weight [over 10 years] hasn't been shown before. I think that if you read the study, a lot of good stuff came out of it.
I will tell my patients how well the lifestyle management works. But I still will tell them that lifestyle is important, but many times, it needs to come in combination with medication.
My issue is that the trial was cut [short]. They saw that other aspects improved, and they should have continued to see what it means. It's like anything; we want fast solution to long-term tissues. Maybe we need to see a population study over 25 or 30 years.
Dr. Yehuda Handelsman is the medical director and principal investigator of Metabolic Institute of America, and president-elect of the American College of Endocrinology. He is on the advisory board for Clinical Endocrinology News.
I think the trial has a good message: that lifestyle can work, that intervention can work, that education can work, but it's not the only solution. For many people with diabetes, we must use medication. And, in many people with coronary disease, we must use medications. But to call it a failed trial is ridiculous, in my mind. If I can delay complications by 4 or 5 years, then we did well, we saved money, and we improved somebody's life.
We saw a 6% reduction in weight over 10 years. This is awesome and has never been shown before. Actually 3.5% reduction in weight [over 10 years] hasn't been shown before. I think that if you read the study, a lot of good stuff came out of it.
I will tell my patients how well the lifestyle management works. But I still will tell them that lifestyle is important, but many times, it needs to come in combination with medication.
My issue is that the trial was cut [short]. They saw that other aspects improved, and they should have continued to see what it means. It's like anything; we want fast solution to long-term tissues. Maybe we need to see a population study over 25 or 30 years.
Dr. Yehuda Handelsman is the medical director and principal investigator of Metabolic Institute of America, and president-elect of the American College of Endocrinology. He is on the advisory board for Clinical Endocrinology News.
CHICAGO – A decade of diet and exercise had no effect on cardiovascular morbidity and mortality in overweight and obese adults with type 2 diabetes, according to a randomized, federally funded study that was stopped 2 years early due to futility.
"However, there are many reasons why, I would argue, that you should be encouraging patients with diabetes to lose weight," said Rena R. Wing, Ph.D., the trial’s chair. The results showed that the participants who were in the diet and exercise group, "are less likely to have kidney disease, have less incidence of depression, lower hospital costs, and less medication costs, so there are still many advantages to intense lifestyle interventions," Dr. Wing said during the presentation of the findings at the annual scientific sessions of the American Diabetes Association.
The results also showed that the participants were able to maintain a modest weight loss during a 10-year period.
The Look AHEAD (Action for Health in Diabetes) trial aimed to fill a gap in existing data about whether intensive lifestyle intervention would decrease cardiovascular morbidity and mortality of patients with type 2 diabetes in the long term.
Researchers recruited more than 5,100 patients and randomized them to the intensive lifestyle intervention program, which decreased calorie intake and increased exercise, or to the control group, which provided diabetes support and education. The goal of the intervention was achieving and maintaining weight loss of at least 7% through group and individual counseling.
The trial’s primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. The trial was planned to have a greater than 80% probability of detecting an 18% difference in cardiovascular events between the two arms, assuming that two-sided alpha was 0.05, a primary outcome rate of 2% per year in the control group, and the planned maximum follow-up of 13.5 years.
But in September 2012, the trial was stopped at the request of its primary sponsors, based on a futility analysis. The median follow-up at the time was 9.6 years.
By then, 403 patients in the intervention group and 418 patients in the control group had met the trial’s primary outcome, with no statistically significant difference between the two groups (1.83 and 1.92 events per 100 person-years, respectively).
Why didn’t it work?
Researchers listed several possible explanations for the results. The study may have had insufficient power, although that wouldn’t explain the negative results, the authors wrote. It is also possible that a higher sustained weight loss was needed in the intervention group to reduce the risk of cardiovascular disease. Meanwhile, the educational sessions and increased use of statins in the control group may have lessened the difference between the two groups, the authors noted. And intensified medical management of cardiovascular risk factors for both groups may have made the relative benefit of the intensive lifestyle intervention more difficult to demonstrate, they added.
Earlier intervention during the course of diabetes may be needed, they added. The results were published online simultaneously with the presentation (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMoa1212914]).
In an editorial accompanying the published results, Dr. Hertzel C. Gerstein wrote that the inclusion of "the somewhat unreliable outcome of hospitalization for angina in the primary composite outcome may have added noise and further obscured any emerging signal" (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMe1306987]).
During the presentation, an audience member suggested that since the 1-year and 4-year findings of the trial were published and well publicized, the participants in the control group might have taken it upon themselves to take action and lose weight. The panel of investigators said that is also a possibility.
Dr. Peter H. Bennett, who is one of the trial’s investigators and was cochair of eligibility, said that stopping the trial "was a big mistake," and that it should have been carried on at least until the planned termination point. "They stopped this trial because they were projecting that if they carried on for 2 more years, the differences in the primary endpoint were unlikely to be statistically significant. But there are several problems. First, you prejudice the power to analyze any other events, and just as we’ve learned from natural history of diabetes-related mortality, it’s clear that you don’t see excess diabetes-related mortality until they’ve had at least 15 years of diabetes, and that’s just at the point that the trial was stopped," Dr. Bennett, scientist emeritus at the National Institutes of Health – one of the main funders of the trial – said in an interview.
"It is also possible that lifestyle interventions may have a real but modest effect on cardiovascular outcomes akin to that of glucose lowering (e.g., a 10%-15% reduction) that requires more than 10 years to become apparent. If so, this trial was clearly too small to detect such an effect," wrote Dr. Gerstein, an endocrinologist and professor at McMaster University and Hamilton Health Sciences, Hamilton, Ont.
A look at the data
The patients in the intervention group (2,570) and control group (2,575) had similar characteristics at baseline. They were between 45 and 75 years old, were mostly female (60%) and white (63%), and had a mean body mass index of 36.0. Fourteen percent had a history of cardiovascular disease, and the median duration of diabetes was 5 years. Less than 30% were on insulin.
Close to 96% of the patients stayed in the trial.
During months 1 and 6, the intervention group had weekly contact with staff members. The contact was gradually reduced in the following months to one on-site individual session per month, and one phone call or e-mail per month from 2 years onward. The patients’ medications were adjusted by their own physicians.
Patients in the control group had 3-4 meetings per year during years 1 through 4, and after that, they had one meeting per year. They received education on diet, exercise, and social support.
Weight loss was greater in the intervention group compared with the control group, with the greatest difference at 1 year (8.6% vs. 0.7%), but it remained significant through the end of the study (6.0% vs. 3.5%).
Specifically, the intervention group had an initial weight loss of 8.6%, followed by weight regain in the first 5 years, and then gradual weight loss, leading to average weight loss of 6%. The control group had a gradual but consistent weight loss, for an average of 3.5% at the end of the trial.
One audience member suggested that some of the weight loss might have been due to aging. The authors said they are looking at those factors in their ongoing data analysis, which they’re planning to publish in the near future.
Meanwhile, the intervention group had significantly greater weight loss than did the control group throughout the trial. They had significantly greater improvements in fitness, hemoglobin A1c levels, systolic blood pressure, and HDL cholesterol (P less than .05 for all). The control group had significantly greater reductions in LDL cholesterol (P less than .05), although they also had a significantly greater use of medications, including insulin, statins, and antihypertensives, compared with the intervention group, the authors noted.
In the short-term (1-4 years), the intervention group saw improvements in cardiovascular risk factors, preservation of mobility, and improvements in fitness, obstructive sleep apnea, fatty liver disease, urinary incontinence, sexual function, and markers of inflammation.
The intervention also reduced the incidence of high-risk chronic kidney disease by 31%, and reduced the total costs and service utilization, especially related to hospitalization ($2,500 per participant), and medication ($2,500 per participant), the authors reported. Although the intervention didn’t affect neuropathy symptoms, it reduced the incidence of reported retinopathy by 14%, reduced the incidence of symptoms of mild or greater depression by 20%, and slowed age-related decline in reported physical function.
Program reduced burden of diabetes
"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 approach as one of the foundations of modern diabetes care," Dr. Gerstein wrote in his editorial, adding that the data show "intensive lifestyle interventions are unlikely to cause harm and may provide a modest benefit."
Interactions among subgroups – history of cardiovascular disease at baseline, and gender, race/ethnicity – showed nonsignificant interaction with cardiovascular disease history (P = .06).
Summarizing the study’s limitations, the authors said that it’s not clear whether changing the intervention groups’ dietary composition might have yielded different results. Their diet during the intervention was 1,200 to 1,800 kcal/day, with less than 30% of calories from fat, and less than 15% from protein. Authors added that the patients recruited successfully competed the fitness test at baseline, so the results can’t be generalized to all patients with type 2 diabetes.
Although the intervention has stopped, the trial continues as an observational study, said Dr. Wing. And some wonder if longer-term results would reveal new information.
"My prediction is that even after stopping the trial, as long as follow-up is carried on for several more years, you’ll see differences in total mortality," said Dr. Bennett, citing the results of UK Prospective Diabetes Study (UKPDS), which showed no difference in cardiovascular disease at 12 years, but a significant difference at 20 years. "So it does appear that intervention does have a lasting but delayed effect on that endpoint."
"I hope [the results] are not misinterpreted," Dr. Bennett continued. "There’s a danger given the lack of effect of the primary endpoint that the headlines will say weight loss is useless, and that’s a total misinterpretation in my view. There are multiple reasons to encourage weight loss. Other than the fact that it doesn’t appear to affect mortality up to this point, it seems to have benefit for all sorts of other things – people feel better, walk better, they develop advanced renal disease less frequently, their cholesterol and blood pressure are lower. I hope that message gets through rather than the negative one."
Dr. Wing, Dr. Bennett, and Dr. Gerstein had no disclosures relevant to the trial. The trial was supported by the National Institutes of Health, other Department of Health and Human Services agencies, and several companies including FedEx, Johnson & Johnson, Nestle Healthcare Nutrition, and Abbott Nutrition.
On Twitter @NaseemSMiller
CHICAGO – A decade of diet and exercise had no effect on cardiovascular morbidity and mortality in overweight and obese adults with type 2 diabetes, according to a randomized, federally funded study that was stopped 2 years early due to futility.
"However, there are many reasons why, I would argue, that you should be encouraging patients with diabetes to lose weight," said Rena R. Wing, Ph.D., the trial’s chair. The results showed that the participants who were in the diet and exercise group, "are less likely to have kidney disease, have less incidence of depression, lower hospital costs, and less medication costs, so there are still many advantages to intense lifestyle interventions," Dr. Wing said during the presentation of the findings at the annual scientific sessions of the American Diabetes Association.
The results also showed that the participants were able to maintain a modest weight loss during a 10-year period.
The Look AHEAD (Action for Health in Diabetes) trial aimed to fill a gap in existing data about whether intensive lifestyle intervention would decrease cardiovascular morbidity and mortality of patients with type 2 diabetes in the long term.
Researchers recruited more than 5,100 patients and randomized them to the intensive lifestyle intervention program, which decreased calorie intake and increased exercise, or to the control group, which provided diabetes support and education. The goal of the intervention was achieving and maintaining weight loss of at least 7% through group and individual counseling.
The trial’s primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. The trial was planned to have a greater than 80% probability of detecting an 18% difference in cardiovascular events between the two arms, assuming that two-sided alpha was 0.05, a primary outcome rate of 2% per year in the control group, and the planned maximum follow-up of 13.5 years.
But in September 2012, the trial was stopped at the request of its primary sponsors, based on a futility analysis. The median follow-up at the time was 9.6 years.
By then, 403 patients in the intervention group and 418 patients in the control group had met the trial’s primary outcome, with no statistically significant difference between the two groups (1.83 and 1.92 events per 100 person-years, respectively).
Why didn’t it work?
Researchers listed several possible explanations for the results. The study may have had insufficient power, although that wouldn’t explain the negative results, the authors wrote. It is also possible that a higher sustained weight loss was needed in the intervention group to reduce the risk of cardiovascular disease. Meanwhile, the educational sessions and increased use of statins in the control group may have lessened the difference between the two groups, the authors noted. And intensified medical management of cardiovascular risk factors for both groups may have made the relative benefit of the intensive lifestyle intervention more difficult to demonstrate, they added.
Earlier intervention during the course of diabetes may be needed, they added. The results were published online simultaneously with the presentation (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMoa1212914]).
In an editorial accompanying the published results, Dr. Hertzel C. Gerstein wrote that the inclusion of "the somewhat unreliable outcome of hospitalization for angina in the primary composite outcome may have added noise and further obscured any emerging signal" (N. Engl. J. Med. 2013 June 24 [doi:10.1056/NEJMe1306987]).
During the presentation, an audience member suggested that since the 1-year and 4-year findings of the trial were published and well publicized, the participants in the control group might have taken it upon themselves to take action and lose weight. The panel of investigators said that is also a possibility.
Dr. Peter H. Bennett, who is one of the trial’s investigators and was cochair of eligibility, said that stopping the trial "was a big mistake," and that it should have been carried on at least until the planned termination point. "They stopped this trial because they were projecting that if they carried on for 2 more years, the differences in the primary endpoint were unlikely to be statistically significant. But there are several problems. First, you prejudice the power to analyze any other events, and just as we’ve learned from natural history of diabetes-related mortality, it’s clear that you don’t see excess diabetes-related mortality until they’ve had at least 15 years of diabetes, and that’s just at the point that the trial was stopped," Dr. Bennett, scientist emeritus at the National Institutes of Health – one of the main funders of the trial – said in an interview.
"It is also possible that lifestyle interventions may have a real but modest effect on cardiovascular outcomes akin to that of glucose lowering (e.g., a 10%-15% reduction) that requires more than 10 years to become apparent. If so, this trial was clearly too small to detect such an effect," wrote Dr. Gerstein, an endocrinologist and professor at McMaster University and Hamilton Health Sciences, Hamilton, Ont.
A look at the data
The patients in the intervention group (2,570) and control group (2,575) had similar characteristics at baseline. They were between 45 and 75 years old, were mostly female (60%) and white (63%), and had a mean body mass index of 36.0. Fourteen percent had a history of cardiovascular disease, and the median duration of diabetes was 5 years. Less than 30% were on insulin.
Close to 96% of the patients stayed in the trial.
During months 1 and 6, the intervention group had weekly contact with staff members. The contact was gradually reduced in the following months to one on-site individual session per month, and one phone call or e-mail per month from 2 years onward. The patients’ medications were adjusted by their own physicians.
Patients in the control group had 3-4 meetings per year during years 1 through 4, and after that, they had one meeting per year. They received education on diet, exercise, and social support.
Weight loss was greater in the intervention group compared with the control group, with the greatest difference at 1 year (8.6% vs. 0.7%), but it remained significant through the end of the study (6.0% vs. 3.5%).
Specifically, the intervention group had an initial weight loss of 8.6%, followed by weight regain in the first 5 years, and then gradual weight loss, leading to average weight loss of 6%. The control group had a gradual but consistent weight loss, for an average of 3.5% at the end of the trial.
One audience member suggested that some of the weight loss might have been due to aging. The authors said they are looking at those factors in their ongoing data analysis, which they’re planning to publish in the near future.
Meanwhile, the intervention group had significantly greater weight loss than did the control group throughout the trial. They had significantly greater improvements in fitness, hemoglobin A1c levels, systolic blood pressure, and HDL cholesterol (P less than .05 for all). The control group had significantly greater reductions in LDL cholesterol (P less than .05), although they also had a significantly greater use of medications, including insulin, statins, and antihypertensives, compared with the intervention group, the authors noted.
In the short-term (1-4 years), the intervention group saw improvements in cardiovascular risk factors, preservation of mobility, and improvements in fitness, obstructive sleep apnea, fatty liver disease, urinary incontinence, sexual function, and markers of inflammation.
The intervention also reduced the incidence of high-risk chronic kidney disease by 31%, and reduced the total costs and service utilization, especially related to hospitalization ($2,500 per participant), and medication ($2,500 per participant), the authors reported. Although the intervention didn’t affect neuropathy symptoms, it reduced the incidence of reported retinopathy by 14%, reduced the incidence of symptoms of mild or greater depression by 20%, and slowed age-related decline in reported physical function.
Program reduced burden of diabetes
"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 approach as one of the foundations of modern diabetes care," Dr. Gerstein wrote in his editorial, adding that the data show "intensive lifestyle interventions are unlikely to cause harm and may provide a modest benefit."
Interactions among subgroups – history of cardiovascular disease at baseline, and gender, race/ethnicity – showed nonsignificant interaction with cardiovascular disease history (P = .06).
Summarizing the study’s limitations, the authors said that it’s not clear whether changing the intervention groups’ dietary composition might have yielded different results. Their diet during the intervention was 1,200 to 1,800 kcal/day, with less than 30% of calories from fat, and less than 15% from protein. Authors added that the patients recruited successfully competed the fitness test at baseline, so the results can’t be generalized to all patients with type 2 diabetes.
Although the intervention has stopped, the trial continues as an observational study, said Dr. Wing. And some wonder if longer-term results would reveal new information.
"My prediction is that even after stopping the trial, as long as follow-up is carried on for several more years, you’ll see differences in total mortality," said Dr. Bennett, citing the results of UK Prospective Diabetes Study (UKPDS), which showed no difference in cardiovascular disease at 12 years, but a significant difference at 20 years. "So it does appear that intervention does have a lasting but delayed effect on that endpoint."
"I hope [the results] are not misinterpreted," Dr. Bennett continued. "There’s a danger given the lack of effect of the primary endpoint that the headlines will say weight loss is useless, and that’s a total misinterpretation in my view. There are multiple reasons to encourage weight loss. Other than the fact that it doesn’t appear to affect mortality up to this point, it seems to have benefit for all sorts of other things – people feel better, walk better, they develop advanced renal disease less frequently, their cholesterol and blood pressure are lower. I hope that message gets through rather than the negative one."
Dr. Wing, Dr. Bennett, and Dr. Gerstein had no disclosures relevant to the trial. The trial was supported by the National Institutes of Health, other Department of Health and Human Services agencies, and several companies including FedEx, Johnson & Johnson, Nestle Healthcare Nutrition, and Abbott Nutrition.
On Twitter @NaseemSMiller
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Major finding: A total of 403 patients in the intervention group and 418 patients in the control group had met the trial’s primary outcome, with no statistically significant difference between the two groups (1.83 and 1.92 events per 100 person-years, respectively).
Data source: Look AHEAD, a study that randomized 5,100 U.S. overweight or obese patients with type 2 diabetes to an intensive weight-loss and physical activity intervention or diabetes support and education.
Disclosures: Dr. Wing, Dr. Bennett, and Dr. Gerstein had no disclosures relevant to the trial.
