Transcript Slide 1

Look AHEAD Study
Lukasz Materek
Endocrinology Rounds
May 20, 2012
Objectives
• Review the Look AHEAD study design
• Understand the outcome measures
• Review currently available evidence and
implications in clinical practice
Background
• Overweight and obesity are major health
problems in the United States, affecting more
than 50% of adults, with 22.5% classified as
obese (body mass index > 30 kg/m2)
• Long-term consequences of being overweight
include increased mortality and increased
morbidity
Look AHEAD Objective
• Assess the long-term effects of an intensive
lifestyle intervention program designed to
achieve and maintain weight loss by
decreased caloric intake and increased
physical activity
• Population: overweight volunteers with type 2
diabetes
Study Population
• ~ 5,000 volunteers with type 2 diabetes
• 45-75 years of age
• overweight or obese (body mass index > 25
kg/m2)
• Potential volunteers who are unlikely to be
able to carry out the components of the
weight loss intervention will be excluded
Study Interventions
• Intensive lifestyle intervention or to diabetes
support and education
• Treatment assignments are unmasked
• Lifestyle intervention is implemented with
individual supervision and group sessions and is
aimed at achieving and maintaining:
– at least a 7% decrease in weight from baseline and
– 175 minutes per week in physical activity
•
• implemented during a four-year period
• most intensive application during the first year
• less frequent attention during the next three
years
• minimum of twice yearly contacts during an
extended follow-up period
Control
• Participants assigned to diabetes support and
education are offered three sessions each year
in diabetes management and social support
Intervention
• variety of diet strategies (e.g. prepared meals
and liquid formula), exercise strategies, and
optional weight loss medications are utilized
Outcomes
• primary outcome is the aggregate occurrence
of major cardiovascular events
– fatal and non-fatal myocardial infarctions
– strokes
– hospitalizations for angina
– cardiovascular deaths over a planned follow-up
period of up to 13.5 years
• Three composite secondary outcomes have also been
defined:
• 1. cardiovascular deaths, myocardial infarctions (fatal
or non- fatal), and strokes (fatal or non-fatal)
• 2. deaths (all causes), myocardial infarctions, strokes,
and hospitalizations for angina
• 3. deaths (all causes), myocardial infarctions, strokes,
hospitalizations for angina, coronary artery bypass
graftings, percutaneous coronary angioplasty,
hospitalizations for congestive heart failure, carotid
endarterectomies, or peripheral vascular procedures
such as bypass or angioplasty
Design
• The study is a two-armed randomized,
controlled clinical trial
• With 5,000 participants, the study has a >80%
probability of detecting an 18% difference in
major cardiovascular disease events between
the two intervention groups
Design Modification
• actual event rate in the Diabetes Support and
Education group was about 0.7% per year
• trial lacked the statistical power necessary to
detect the originally hypothesized effect
• primary endpoint was expanded to include
hospitalized angina and the duration of the
trial should be increased by two years.
Intervention Group
• diet modification and increased physical
activity with a goal of sustained weight loss
• intervention has been designed to allow
individual flexibility of treatment strategies
• portion-controlled diet
• behavioral techniques, diet modification,
physical activity, and social support
Phase I (year 1)
• participants are seen in clinic weekly with three group
meetings and one individual counseling session per
month
• total of 24 visits during the first 26 weeks
• months 7-12, participants are seen in clinic at least
twice a month
• group sessions are provided every-other-week, with
participants encouraged to attend at least one group
meeting per month
• monthly one-on-one meetings with individual
counselors
Phase II (Months 13-48)
• minimum of two contacts per month are
expected during this phase
• refresher groups will be offered once a week
for up to six weeks and will be designed to
reverse weight gain or promote weight
maintenance.
Phase III (Months 49+)
• participants will be offered monthly on-site
individual contact with a counselor
• open groups will be offered one time per
month
Goals
Diet
• restriction of caloric intake is the primary
method of achieving weight loss
– 1200-1500 kcal/day for individuals weighing 250
lbs (114 kg) or less at baseline
– 1500-1800 kcal/day for individuals who weigh
more than 250 lbs
– These goals can be reduced to 1000-1200 kcal/day
and 1200-1500 kcal/day, respectively, if
participants do not lose weight
– These calorie levels should promote a weight loss
of approximately one to two lbs/week
Diet
• maximum of 30% of total calories from total
fat
• maximum of 10% of total calories from
saturated fat
• minimum of 15% of total calories from protein
• Portion-controlled diets provide patients
servings of food with a fixed calorie and
macronutrient content
• Participants choose from two prototype diets
Diet Option 1
• commercially available liquid meal
replacement that will replace two meals and
snacks each day
• evening meal of either a frozen entrée or
conventional table foods to provide a total of
1200-1800 kcal/day depending on the
individual’s baseline weight
Diet Option 2
• consumption of a very structured meal plan,
with the same calorie range, using foods that
participants prepare themselves
• for those who do not accept or tolerate the
liquid/prepared meal prototypes
Activity
• unsupervised exercise, with gradual
progression toward a goal of 175 minutes of
moderate intensity physical activity per week
by the end of the first six months
• Moderate-intensity walking is encouraged as
the primary type of physical activity
Activity
• Exercise bouts of ten minutes and longer are
counted toward this goal
• Exercise is recommended to occur five days
per week
• occupational activity will not be counted
towards the physical activity goal
Cognitive Behavioral Strategies
• training in cognitive behavioral strategies to
help produce and maintain changes in dietary
intake and physical activity
Further Strategies
• After six months of lifestyle strategies alone, a
toolbox of weight loss medications and
advanced behavioral strategies may also be
employed
• Drugs are used only as an adjunct to an
intensive program of exercise and dietary
modification
• Only drugs that have received FDA approval
for use in weight loss are included
• only drug originally approved for the toolbox
was orlistat, however it was later voted to
discontinue its use based on finding limited
effectiveness
• primary analyses in this article examined the
relationships between categories of weight loss
and changes in CVD risk factors
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weight changes from baseline to 1 year:
gained >2%
remained weight stable (±2%)
lost ≥2 to <5%
lost ≥5 to <10%
lost ≥10 to <15%
lost ≥15%.
Baseline Charecteristics
• ILI participants had a weight loss (means ± SD)
of 8.7 ± 7.6 kg compared with 0.8 ± 5.0 kg in
the DSE group (P < 0.0001)
Table 1
• 60% of the participants were women, and 37%
were from ethnic or racial minority groups.
Participants were an average age of 58.7 ± 6.8
years and weighed 100.7 ± 19.3 kg at study
entry.
• Weight changes were significantly correlated
with changes in glycemic control, blood
pressure, HDL cholesterol, and triglycerides
• greater the weight change, the greater the
improvements in each risk factor in the full
cohort and within the ILI and DSE group
separately
A1C
Fasting Glucose
BP
TG
HDL and LDL
Lipid Profile – not on medications
• six weight change categories, adjusted for age,
sex, race, treatment group assignment,
baseline weight, and baseline level of the risk
factor
• strong graded association was seen for
changes in glucose, HbA1c, SBP, DBP,
triglycerides, and HDL cholesterol (all P values
<0.0001).
• magnitude of improvement in LDL cholesterol
did not differ across the weight categories,
even in those not using lipid-lowering
medications at baseline and 1 year
TG 0.5; LDL 0.25; HDL 0.13; glucose 1.1
Conclusion
• modest weight losses of 5–10% of initial
weight are sufficient to produce significant,
clinically relevant improvements in CVD risk
factors in overweight and obese patients with
type 2 diabetes
• examined effects at 1 year only
Conclusion
• The magnitude of weight loss at 1 year was
highly related to the improvements in blood
pressure, glycemic control, and lipids, with the
notable exception of LDL cholesterol
• assessment of the associations that weightloss patterns during the first year of an
intensive lifestyle intervention have with 4year maintenance and health outcomes
Conclusions
• Greater month-to-month weight losses and
more gradual and sustained weight losses
during the 1st year were each associated with
better longer term weight loss
• Associations were independent of each other
and of a panel of participant characteristics:
markers of demography, health, and lifestyle,
including baseline BMI and diabetes control
Conclusions
• weight loss that is achieved through gradual
and sustained increments, rather than a more
rapid loss weight loss that is not sustained, is
associated with better long-term maintenance
• Greater month-to-month weight losses during
the 1st year of the weight-loss intervention
were associated with longer term benefits
Conclusions
• Look AHEAD strategy works in severely obese
patients
Conclusions
• Improvement in markers
• Will this translate into mortality/events
outcomes ???
Final Conclusions
• Key:
– weight loss
– diet
– Exercise
• Wait for final results of the Look AHEAD Study
– Completion 2014
Patient Goals
• Weight:
– Weight loss goal: Lose 10% of initial weight
– Continued loss or weight maintenance
• Activity
– Exercise 175 min/wk by month 6
– Increase minutes per week of activity; 10,000
steps/day goal
• Study information including educational
materials published online
• Thanks!