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DM: Prevention and Treatment of CVD (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To compare the effect of orlistat plus diet vs diet alone on vascular risk factors in patients with metabolic syndrome and type 2 diabetes.
Inclusion Criteria:
  • type 2 diabetes
  • age 30-72
  • treated with oral antidiabetic agents
  • met at least 3 of these criteria:
    • waist circumference > 102 cm in men and >88 cm in women
    • triglycerides > 150 mg/dL
    • HDL < 40 mg/dL in men and <50 mg/dL in women
    • blood pressure > 130/85 mmHg
    • fasting glucose >110 mg/dL
Exclusion Criteria:
  • insulin-dependent
  • symptomatic vascular disease
  • total chol > 350 mg/dL or triglycerides > 500 mg/dL
  • HbA1c less than 7.0% or greater than 10.0%
  • major gastro-intestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • history of allergy relevant to the trial
  • concomitant use of drugs that may affect body weight
Description of Study Protocol:

Recruitment :  not specified

Design:  Randomized Controlled Trial

  • subjects randomized so that 3/4 of them were treated with orlistat plus diet and 1/4 were treated with diet alone
  • study duration was two years

Blinding used (if applicable) none

Intervention (if applicable)

  • hypocaloric diet
    • specific 7-day diet sheet handed to the patient at every visit
    • calorie intake set at 500 calories below needs of the patient
    • compliance measured by patient returning the diet sheets to the investigating physician

Statistical Analysis

  • study model was a factor repeated measures design over time (6 months)
  • analysis of covariance to investigate the significance of changes within and between treatment groups over time
  • ANOVA
  • paired t test
  • Wolcoxon signed rank sum test
  • Sign test
  • Pearson correlation coefficient
  • Cochran-Mantel-Haenszel test
  • chi-square test

 

Data Collection Summary:

Timing of Measurements:  physical exam every 4 weeks and laboratory tests every 8 weeks

Dependent Variables

  • body weight
  • waist circumference
  • blood pressure
  • lipid profile
  • fasting glucose, by GOD-PAP method using an Olympus autoanalyzer
  • fasting insulin
  • homeostasis model for assessment of insulin resistance (HOMA)
  • HbA1c

Independent Variables: 

  • orlistat plus hypocaloric diet vs hypocaloric diet alone
  • compliance was assessed as diet sheets were returned to investigators

Control Variables

 

Description of Actual Data Sample:

Initial N:126, 32% male

Attrition (final N):  no patient excluded from the analysis because this was an intent-to-treat study; 1 patient dropped out due to intolerance of orlistat

Age: 57±11 y for diet only group; NS difference from orlistat+diet group

Ethnicity: not specified

Other relevant demographics: known duration of diabetes 8.9±6.4 for diet only group; NS difference from orlistat+diet group

Anthropometrics:  no significant differences between groups

Location: Greece

 

Summary of Results:

 

Variables

hypocaloric diet

orlistat + hypocaloric diet

 orlistat + diet vs diet 6th  month p value(ANCOVA)

 

 baseline  6 months p value baseline  6 months  p value  

Body weight, kg

 87.3±12.0

  83.4±8.8  0.075

 93.4±15.2

  87.8±14.6  <0.0001  0.0001

Waist circumference, cm

 105±11

  102±8  0.092

 112±11

  103±11  <0.0001  <0.0001
 Glucose, mmol/l  9.7±2.3  9.6±2.8  0.79  10.0±2.9  7.5±2.0  <0.0001 <0.0001
 Insulin, micro-mol/l  17.1±13.2  17.5±16.0  0.52  24.0±16.8  22.2±21.9  0.75  0.31
 HOMA index (insulin resistance)  0.56±0.05  0.55±0.05  0.77  0.42±0.04  0.34±0.03  0.004

 0.022
 HbA1c, %  7.9±0.7  7.1±1.3  0.0001  8.0±0.9  6.4±1.0  <0.0001  <0.0001
 cholesterol, mmol/l  5.8±1.1  5.7±1.1  0.85  5.7±1.1  5.1±1.0  <0.0001  <0.0001
 LDL, mmol/l  3.8±1.0  3.7±1.1  0.83  3.6±1.2  3.1±0.9  0.003  0.0345
 non-HDL cholesterol, mmol/l

 4.6±1.0

  4.5±1.0  0.72  4.5±1.1  3.9±1.0

 0.004

  0.037
 triglycerides  1.8±0.6  1.7±0.7  0.70  2.0±0.9  1.7±0.8  0.18  0.32
 HDL  1.2±0.3  1.2±0.2  0.10  1.2±0.2  1.2±0.3  0.36  0.41
serum uric acid, micromol/l  418±61  372±54  0.005  429±57  313±38  <0.0001  0.0002
 systolic BP  139±16  136±17  0.55  138±20  130±15  0.002  0.024
 diastolic BP  78±7.0  79±7.0  0.23  81±8.0  78±7.5  0.04  0.27
10-yr risk, %  15.6±4.2  14.9±4.4  0.78  15.8±4.5  7.9±2.6  <0.0001  <0.0001

Other Findings

  •  At the 6th treatment month, the mean weight loss was significantly greater with orlistat compared with diet alone (-6% vs -2.5%, p <0.0001). 
  • More orlistat-treated patients than those on diet alone maintained a weight loss of more than 5% (67% vs. 19%, p<0.0001).
  • At the end of 6 months follow-up 35% of patients on orlistat  plus diet no longer satisfied the criteria for metabolic syndrome vs 9% of patients on diet alone (P<0.0001)
Author Conclusion:
Weight management involving orlistat resulted in significant weight loss, improved glycemic control and vascular risk factor profile in patients with metabolic syndrome and type 2 diabetes.  Orlistat reduced the number of metabolic syndrome components and the calculated vascular risk.  Orlistat should be considered as an option for treatment of these patients.  The results need to be confirmed by larger trials.
Funding Source:
Reviewer Comments:

Study duration was 2 years, but individual patient data was collected over a period of 6 months.  No dietary assessment was reported for either group.  It's unclear how compliance to the diet was assessed using the diet sheets.

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? 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? 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? No
  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? No
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  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? N/A
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