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Weight Management

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To assess the long-term effects of orlistat on body weight, glycemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.
Inclusion Criteria:
  • men & women aged 18 - 70yrs
  • BMI > 28 kg/m2
  • HbA1C 6.5 - 11%
  • type 2 diabetes diagnosis
Exclusion Criteria:
  • Patients treated with antidiabetic drugs other than sulphonylureas
  • Patients treated with medications known to affect body weight, serum lipids, or vitamins
  • any other chronic disease such as: cardiac, renal, hepatic, gastrointestional, psychiatric, immunological or metabolic disorders.
  • Females who were pregnant, lactating, or at risk of becoming pregnant
Description of Study Protocol:

Recruitment

Subjects were recruited at 58 primary care physician and outpatient clinics in Germany. 

Design

Multicenter, Randomized, Placebo-Controlled Trial.

Blinding used (if applicable)

Single blinding during lead in period & double blinding during intervention period.

Intervention (if applicable)

After screening, eligible patients entered a 4 week lead in period before being randomized into one of the following groups:

treatment group: orlistat TID with main meals for 48 weeks

control group: placebo TID with main meals for 48 weeks

Patients were then placed on a diet consisting of: 30% calories from fat, 50% calories from carbohydrate and 20% calories from protein. Diet prescriptions were based on estimates of maintenance needs < 600 kcal/day to promote 0.25-0.50kg/week of weight loss by week 24. Patients were required to consume a minimum of 1200 kcal/day.

Statistical Analysis

Efficacy was assessed on an intent-to-treat basis. Power calculations indicated that 100 evaluable patients per treatment group would be needed to detect a mean difference of 3 kg between the orlistat and placebo groups with a power of 80% at the two-sided significance level of 5%. All values are + SD.

 

Data Collection Summary:

Timing of Measurements

  • body weight, fasting glucose, patient's medication and vital signs were assessed at weeks: -4, -2, 0, and at 4 week intervals up until 48 weeks.
  • HbA1C, post-prandial glucose and lipid profile were assessed at weeks: -4, 0 and 48.
  • blood chemistry and complete blood counts were assessed at weeks: -4, 24 and 48.
  • serum creatinine and vitamins D, E and beta carotene were assessed at weeks: -4, 0, 12, 24, 36 and 48.

Dependent Variables

  • change in body weight (kg)
  • glycemic control
  • waist circumference
  • lipid profile
  • systolic and diastolic blood pressure

Independent Variables

  • orlistat or placebo TID with main meals for 48 weeks - compliance assessed by counting number of capsules returned and patients were considered compliant if they took at least 75% of medication 
  • diet: 30% calories from fat, 50% calories from carbohydrate, 20% calories from protein 

 Control Variables

Description of Actual Data Sample:

Initial N: Total study population of 340 was planned. 170 per group would allow for dropout rate of 40%.  492 were enrolled in lead-in period, and 383 were randomized to treatment (195 in orlistat group, 188 in placebo group).  109 were not randomized due to violation of selection criteria, other protocol violation, refused treatment, failure to return, did not cooperate, adverse event, and other reasons.

Attrition (final N): 369 subjects.  189 in orlistat group (91 male, 98 female), 180 in placebo group (90 male, 90 female), 4% dropout rate

Age: placebo group: 55.8 + 8.9, orlistat group: 56.6 + 8.6

Ethnicity: not given

Other relevant demographics: N/A

Anthropometrics: placebo and orlistat groups had similiar characteristics for: weight, BMI, waist circumference, HbA1C, lipid profile, and blood pressure. 

Location: Germany

 

Summary of Results:

 

Variables

Orlistat Group

Placebo Group

P value

weight loss (kg after 1 year)

5.3 + 5.1

3.4 + 5.3

P= 0.006

HbA1C (decrease after 1 year)

 0.9 + 1.3%

 0.4 + 1.5%

P= 0.0003

fasting glucose (mmol/l)

 -1.6 + 2.5

 -0.7 + 3.2

P= 0.004
2 hour post-prandial glucose concentrations (mmol/l) -1.8 + 3.8 -0.5 + 4.6 P= 0.003
Total Cholesterol -2.3 + 16.3% +1.8 + 22.0% P< 0.01
LDL -2.0 + 26.7% +5.1 + 34.3% P<0.05
HDL (increase in level) 0.6 + 20.0% 6.4 + 24.5% P < 0.01

Other Findings

  • No significant changes in triglycerides or reduction in systolic or diastolic blood pressure between the groups.
  • For the subgroup of type 2 diabetic patients who were treated with diet alone, greater weight loss and improved glycemic control was seen in the orlistat group compared to placebo group, however; the results were not statistically significant with the exception of waist circumference ( p< 0.05).

 

 

Author Conclusion:
Treatment with orlistat plus diet resulted in significant weight loss, improved glycemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.
Funding Source:
Industry:
Hoffman LaRoche
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
Compliance assessed.  Low dropout rate after 1 year.
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) No
  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? N/A
  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