EAL

Weight Management

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The objective of the study was to compare standard therapy weight loss program with one that also employed a pharmacologic agent (sibutramine) and meal replacement products.

Inclusion Criteria:

ages 30 to 70
obesity with BMI 27-50 kg/m2; stable weight for previous 3 months
type 2 diabetes diagnosis with HbA_1c 7.0 - 10.0%
constant doses of any oral diabetes, hypertension, and lipid medications for at least 1 months
gave informed consent

Exclusion Criteria:

age not within range of 30 to 70 years
current use or use of insulin in previous 6 months
prior use of sibutramine
use of any weight loss product or participation in any formal weight loss program in the previous month
signicant abnormality on screening tests
history of heart disease or stroke
prior bariatric surgery
lactose intolerance
any chronic disease or therapy that would make adherence to study protocol difficult

Description of Study Protocol:

Recruitment: not described, but subjects were screened and randomized at University of Minnesota General Clinical Research Center

Design: Randomized Controlled Trial (randomization stratified by gender)

Blinding used: study coordinator blinded to randomization schedule

Intervention:

Standard therapy included:

Energy level of diet: calculated by dietitian based on calculated basal energy requirement and rmeasured resting energy expenditure; subject received individualized diet to promote 500 to 1000 kcal daily deficit
Subject received individualized exercise recommendation that included walking 30 minutes three times weekly in addition to usual activity
Educational program of dietary exercise and behavioral strategies to facilitate weight loss

Intervention included standard therapy plus:

10 mg sibutramine daily with option to increase to 15 mg daily after 6 months if BMI > 27 kg/m2
low-calorie diets providing 900-1,300 kcal per day made up exclusively of meal replacement produts for 7 consecutive days every 2 months
between low-calorie diet weeks, use of one meal replacement product and one snack bar daily to replace one usual meal and snack

Statistical Analysis

Intent to treat analysis for subjects who returned for initial follow-up after randomization
Data for subjects who withdrew before 12 months included through last study vsit
Student's t-test used to compare baseline data and 12-month changes
X² test used to compare categorical data
Least squares linear regression used to examine relationship between weight loss and change in HbA_1c
Significance at P < 0.05
Power analysis revealed 30 subjects in each treatment group would yield 90% power to detect difference of 6.2 kg in mean weight loss between groups at alpha = 0.05

Data Collection Summary:

Timing of Measurements

Measurements at baseline and each follow-up visit included: body weight, height, blood pressure, heart rate and blood samples for fasting glucose, lipids, HbA1c.

Body composition assessed at baseline, 2, 6 and 12 months

Follow-up visits

occured after baseline visit at 1 month, 2 months, and every 2 months thereafter for all subjects
in addition, combination therapy group received an additional visit after each low-calorie diet week for emasurement of weight, pulse and blood pressure%

Diabetes medications were initiated or adjusted per preestablished protocol if HbA_1c was > 10.0% or if symptoms of hypoglycemia were present (more than twice per week or home blood glucose values frequently < 80 mg/dl).

Dependent Variables

weight loss (difference after 12 months)
glycemic control (difference in HbA_1c)
blood pressure
pulse rate
fasting plasma lipids

Independent Variables

combination therapy
- sibutramine (10 to 15 mg/day)
- use of meal replacement products

Control Variables

Description of Actual Data Sample:

Initial N: 59 (29 standard therapy 45% male; 30 combination treatment 46% male)

Attrition: 92% of subjects finished 12 months in study (5 subjects withdrew: 2 from standard therapy group and 3 from combination therapy group)

Age:

standard therapy group: 55 ± 5 years
combination therapy group: 52 ± 5 years

Ethnicity: not described

Other relevant demographics: groups did not differ significantly in baseline demographic and clinical data

Anthropometrics

Location: Minnesota

Summary of Results:

Variables	Combination Therapy Group Mean ± SEM	Standard Therapy (control) Group Mean ± SEM	Statistical Significance of Group Difference
Weight Loss	-7.3 ± 1.3 kg	-0.8 ± 0.9 kg	<0.001
Body fat (kg)	-4.6 ± 1.0 kg	-0.1 ± 0.7 kg	<0.001
Blood Glucose Control (decrease in HbA_1c)	0.6 0.3%	no change	< 0.05

There were no significant differences in fasting glucose, lipids, pulse or blood pressure between groups.
Combination therapy resulted in reduced need for diabetic oral medications
5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA1c (P = 0.006)

Other Findings

Author Conclusion:

The weight loss program combining standard treatment with sibutramine and meal replacement products resulted in greater weight loss and improved diabetes control.

Funding Source:

Government:

NIH

Industry:

Abbott Labs, Slim Fast

Food Company:

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

Meal replacement and snack products were provided by Slim Fast. The investigators acknowledged a possible confounding effect of diabetes medications. Unfortunately, they did not design the study so as to be able to determine what caused the increased weight loss: drug use or the meal replacement products.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		No
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	???
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes