DM: Prevention and Treatment of CVD (2007)
- 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
- 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
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
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
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
Variables |
hypocaloric diet |
orlistat + hypocaloric diet |
orlistat + diet vs diet 6th month p value(ANCOVA) |
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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)
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
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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 | |