EAL

Weight Management

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare the effects of orlistat and placebo, in combination with a weight management program, on weight loss and metabolic profile over 1 year.

Inclusion Criteria:

Patients with Type 2 diabetes & receiving treatment with either metformin alone or metformin and sulphonylurea
30-75 years old
BMI 28-40 kg/m²
HbA_1C 6.5-10%

Exclusion Criteria:

treatment with insulin
a recent myocardial infarction
other significant peripheral vascular, cardiac, respiratory, renal, neurological, gastrointestional or endocrine diseases
signs of fat-soluble vitamin deficiencies
patients who were taking: drugs influencing appetite, resins, fish oil supplements and retinoids

Description of Study Protocol:

Recruitment

Patients who were being treated at one of the 16 primary care centers/hospital-based diabetes clinics in Sweden and who fit the above inclusion critera.

Design

A weight management program was initiated for all of the patients two weeks before the randomization with a reduced calorie diet (600 kcal/day deficit) containing 30% from fat and this program was maintained throughout the study. Patients were assigned to a treatment group through a central randomization process, stratified by center, sex and anti-diabetic treatment.

Blinding used (if applicable)

Double blind.

Intervention (if applicable)

Orlistat 120mg or placebo was taken tid with food and dietary counseling was provided by a nurse or dietitian at every study visit. The dietary advice was part of a self-management package for weight control which included leaflets and a food diary. The patients were also encouraged to increase their physical activity with a daily 30 minute walk. Compliance to the pharmocotherapy was assessed on the basis of capsule counts.

Statistical Analysis

Weight loss was calculated as the change from the screening visit (week-2) to week 52. The analysis for covariance for weight loss, the interaction effect between treatment and center was included and with covariates of age, sex, BMI and current smoking status. Chi-squared tests were used for categorical analyses of the frequency distributions of weight. All data was presented as means + SD.

Data Collection Summary:

Timing of Measurements

body weight at every visit
waist circumference at: baseline and weeks 12, 24 and 52
proportion of patients achieving > 10% and > 5% determined at week 52
HbA_1C, fasting plasma glucose and insulin, and pre and post-prandial glucose from patients' self monitoring at: baseline, weeks 12, 24, 40, and 52.
TG, total cholesterol, LDL, and HDL were assessed at: baseline, 12, 24, 40 and 52 weeks
The proportion of patients acheiving > 0.5%, > 0.7% and > 1.0% reduction in HbA_1C level was assessed at week 52.
Changes in anti-diabetic medication were recorded after 52 weeks.

Dependent Variables

HbA_1Cat week 52, HbA_1C (week 52) = 2.62 + 0.65 x HbA_1C at screening - 0.51 x treatment group + 0.12 x weight reduction
change in weight from baseline to week 52

Independent Variables

Placebo vs orlistat, compliance assessed by capsule counts
Weight management program

Control Variables

age
sex
BMI
smoking status

Description of Actual Data Sample:

Initial N: 220 orlistat group: 111, placebo group: 109

Attrition (final N): orlistat group:96 (86%), placebo group: 94 (86%)

Age: Orlistat: 58.9 + 9.1, Placebo: 59.3 + 8.5

Ethnicity: Caucasian

Other relevant demographics:

Anthropometrics

weight(kg): orlistat group: 95.3 + 12.6, placebo group: 95.7 + 12.5
BMI (kg/m²): orlistat group: 32.6 + 3.1, placebo group: 32.9 + 3.0
waist circumference (cm): orlistat group: 108.0 + 9.0, placebo group: 109.0 + 9.3
HbA₁(%): orlistat group: 7.6 + 0.8, placebo group: 7.6 + 0.8

Location: 16 primary care centers and 6 hospital-based diabetes clinics in Sweden

Summary of Results:

Variables (at 52 weeks)	Orlistat Group	Control group	Statistical Significance of Group Difference
% body weight lost	-5%	-1.8%	P<0.0001
weight loss > 5%	n=51	n=12	P<0.001
weight loss > 10%	n=15	n=3	P= 0.0036
weight change in subgroup receiving metformin only	-5.5 + 4.4%	-1.5 + 3.1%	P<0.0001
weight change in subgroup receiving metformin + sukphonylurea	-4.8 + 4.1%	-2.0 + 3.3%	P< 0.0001
mean reduction in waist circumference	108.0 + 9.0 cm to 103.0 + 9.3 cm	109.0 + 9.3 to 106.0 + 9.1 cm	P= 0.0022
mean reduction in HbA_1C	-1.1%	-0.22%	P<0.0001
mean reduction in fasting plasma glucose	-1.9 mmol/l	-0.26 mmol/l	P<0.0001
mean change in total cholesterol	-0.24 + 1.00	0.10 + 1.11	P= 0.0297

Other Findings

mean reduction in blood pressure from baseline to week 52 was similiar in the orlistat and placebo groups, p= 0.89
approximately four times more orlistat treated patients achieved a > 5% decrease in body weight than placebo group
almost five times more orlistat than placebo patients responded with a > 10% weight loss

Author Conclusion:

Orlistat, in combination with a reduced calorie diet and a weight management program, promotes weight loss and clinically relevant improvements in glycaemic control and other cardiovascular risk factors in obese patients with Type 2 diabetes.

Funding Source:

University/Hospital:

University Hospital Uppsala

Reviewer Comments:

A well designed study, but would have liked to see the dietary education come from dietitians only & not nurses.

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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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?	N/A
	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	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?		Yes
	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)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
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