DM: Weight Management (2007)

Citation:

Derosa G, Cicero AF, Murdolo G, Ciccarelli L, Fogari R. Comparison of metabolic effects of orlistat and sibutramine treatment in Type 2 diabetic obese patients. Diabetes Nutr Metab 2004;17:222-229.

PubMed ID: 15575343
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese diabetic patients of both sexes, with specific attention to metabolic pattern-induced changes and cardiovascular effects.
Inclusion Criteria:
  • Adults age 18+ years
  • BMI > 30 kg/m2
  • Type 2 diabetes
  • Diabetic for at least 6 months with glycemic control with diet or oral hypoglycemic agents
  • Normotensive (BP 130/80)
Exclusion Criteria:
  • evidence of ischemic heart disease, heart failure or stroke
  • seated pulse rate > 100 bpm
  • weight change of >3kg during the previous 3 months
  • malignancy
  • signficant neurological or psychiatric disturbances including alcohol & drug abuse
  • renal, hepatic, endocrine or gastrointestinal disorders
  • women who were pregnant, lactating or may become pregnant

 

Description of Study Protocol:

Recruitment

Patients were enrolled, evaluated and followed in 3 Italian Centres of Internal Medicine.  Subjects were identified from review of case notes and/or computerized clinic registers were contacted personally or via telephone.

Design:  Randomized Controlled Trial.  Randomization was done using a drawing of envelopes containing randomization codes prepared by a statistician

Blinding used (if applicable): Double-blind

Intervention (if applicable)

  • Orlistat (360 mg/day) or sibutramine (10 mg/day) for 12 months
  • Randomized after 4 weeks on controlled energy diet (near 600 kcal deficit)
  • Dietitians and/or specialist doctors periodically provided instructions on dietary intake recording procedures as part of a behavior modification program and used the food diaries for counselling
  • During the study there was 1 behavior modification session on weight loss strategies at baseline, 1 at 6 months, and 4 seminars with all patients at 3, 6, 9 and 12 months
  • Physical activity was encouraged but not assessed
  • All vitamin and mineral preparations were discontinued 4 weeks prior to randomization

Statistical Analysis

  • Intent to treat analysis conducted in patients who had received at least 1 dose of medication and had a subsequent efficacy observation
  • ANOVA and ANCOVA used
  • Statistical significance of the independent effects of treatments and weight loss on the other parameters was determined by ANCOVA using weight loss as the covariate
Data Collection Summary:

Timing of Measurements

Before starting the study, patients underwent an initial screening assessment.  Anthropometric variables, glycemic control, blood pressure and heart rate evaluated at baseline and after 3, 6, 9 and 12 months of treatment.

Dependent Variables

  • Body weight, height, BMI
  • HbA1c measured by HPLC method
  • Fasting plasma glucose and postprandial glucose assayed by glucose-oxidase methods
  • Waist circumference, hip circumference, waist:hip ratio
  • Blood pressure 
  • Fat soluble vitamins monitored regularly at central lab
  • Adverse events recorded

Independent Variables

  • Orlistat (360 mg/day) or sibutramine (10 mg/day) for 12 months; compliance assessed using pill counts
  • Randomized after 4 weeks on controlled energy diet (near 600 kcal deficit)
  • Dietitians and/or specialist doctors periodically provided instructions on dietary intake recording procedures as part of a behavior modification program and used the food diaries for counselling
  • During the study there was 1 behavior modification session on weight loss strategies at baseline, 1 at 6 months, and 4 seminars with all patients at 3, 6, 9 and 12 months
  • Physical activity was encouraged but not assessed
  • All vitamin and mineral preparations were discontinued 4 weeks prior to randomization

Control Variables

 

Description of Actual Data Sample:

Initial N: 144 enrolled.  141 randomized (69 males, 72 females), 71 assigned to orlistat (35 males, 36 females) and 70 assigned to sibutramine (34 males, 36 females).

Attrition (final N):   133 completed (65 in orlistat, 68 in sibutramine).  

Age:  mean age 53 +/- 5 years in orlistat group; 51 +/- 4 years in sibutramine group

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:  There were no significant differences between centers in sex distribution, age, diabetes duration, and diabetes treatment.  Baseline characteristics nonsignificant between 2 treatment groups.

Location:  Italy

 

Summary of Results:

 Orlistat Group

Variables

Baseline

3 Months 6 Months 9 Months

12 Months

BMI 33.6 +/- 1.3 31.8 +/- 1.0 30.9 +/- 0.8, P < 0.05 30.3 +/- 0.7, P < 0.02 29.7 +/- 0.6, P < 0.01

Waist circumference (cm)

102 +/- 5

101 +/- 3

100 +/- 4 98 +/- 3

96 +/- 4

Hip circumference (cm) 116 +/- 8 115 +/- 7 114 +/- 6 113 +/- 5 112 +/- 5, P < 0.05
Waist:hip ratio 0.88 +/- 0.2 0.88 +/- 0.2 0.87 +/- 0.1 0.86 +/- 0.1 0.85 +/- 0.05, P < 0.05
HbA1c (%) 7.1 +/- 0.5 6.9 +/- 0.4 6.7 +/- 0.3, P < 0.05 6.5 +/- 0.2, P < 0.02 6.3 +/- 0.3, P < 0.01
Fasting plasma glucose (mg/dl) 135 +/- 16 130 +/- 15 125 +/- 13 122 +/- 12, P < 0.05 120 +/- 10, P < 0.02
Postprandial glucose (mg/dl) 151 +/- 22 146 +/- 20 143 +/- 18 140 +/- 17, P < 0.05 136 +/- 15, P < 0.02
SBP (mmHg) 127 +/- 2 127 +/- 2 125 +/- 3 125 +/- 2 124 +/- 3, P < 0.05
DBP (mmHg) 82 +/- 2 81 +/- 3 82 +/- 2 80 +/- 3 79 +/- 2, P < 0.05

Heart rate (bpm)

74 +/- 5

73 +/- 5

75 +/- 4 74 +/- 6

74 +/- 4

Sibutramine Group

Variables

Baseline

3 Months 6 Months 9 Months

12 Months

BMI 33.1 +/- 1.4 31.4 +/- 1.1 30.4 +/- 0.9, P < 0.05 30.0 +/- 0.8, P < 0.02 29.5 +/- 0.5, P < 0.01

Waist circumference (cm)

101 +/- 4

100 +/- 3

99 +/- 3 97 +/- 4

95 +/- 3, P < 0.05

Hip circumference (cm) 114 +/- 6 113 +/- 5 112 +/- 4 111 +/- 5 110 +/- 4, P < 0.05
Waist:hip ratio 0.89 +/- 0.3 0.88 +/- 0.2 0.88 +/- 0.1 0.87 +/- 0.1 0.86 +/- 0.05, P < 0.05
HbA1c (%) 7.0 +/- 0.6 6.8 +/- 0.5 6.5 +/- 0.4, P < 0.05 6.3 +/- 0.3, P < 0.02 6.1 +/- 0.2, P < 0.01
Fasting plasma glucose (mg/dl) 141 +/- 19 136 +/- 18 130 +/- 15 127 +/- 14, P < 0.05 124 +/- 13, P < 0.02
Postprandial glucose (mg/dl) 155 +/- 25 150 +/- 21 145 +/- 20 142 +/- 19, P < 0.05 139 +/- 18, P < 0.02
SBP (mmHg) 126 +/- 3 127 +/- 3 128 +/- 3 127 +/- 2 128 +/- 3
DBP (mmHg) 81 +/- 3 82 +/- 2 83 +/- 3 83 +/- 3 81 +/- 3

Heart rate (bpm)

73 +/- 6

75 +/- 5

74 +/- 6 75 +/- 5

75 +/- 6

Other Findings

Significant BMI improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups.

Significant waist circumference, hip circumference, and waist:hip ratio improvement was observed after 12 months (p < 0.05) in both groups.

Significant HbA1c decrease was obtained after 6 (p < 0.05), 9 (p < 0.02) and 12 (p < 0.01) months in both groups.

After 9 and 12 months, mean fasting plasma glucose and postprandial plasma glucose levels were significantly decreased in both groups (p < 0.05 and p < 0.02, respectively).

Significant systolic and diastolic blood pressure improvement was present in the orlistat group after 12 months.

No significant change in blood pressure measurements was observed in the sibutramine group during the study.

No significant heart rate variation was obtained during the study in either group.

Of the 133 patients who completed the study, 33.8% of those in the orlistat group and 13.2% of those in the sibutramine group had side effects (p < 0.05 between groups).

Side effect profiles were different in the 2 treatment groups.

All orlistat side effects were gastrointestinal events.

Sibutramine caused an increase in blood pressure in 1 patient, but it was controlled by antihypertensive treatment.

Vitamin changes were small and all mean values remained within reference ranges; no patients required vitamin supplementation.

Author Conclusion:
Both orlistat and sibutramine were effective on anthropometric variables and on metabolic pattern during the 12-month treatment; in our sample, orlistat appears to be slightly more efficacious as an anti-obesity drug, while sibutramine intake was not associated to any cardiovascular effect and was generally better tolerated than orlistat.
Funding Source:
University/Hospital: University of Bologna, University of Perugia
Reviewer Comments:
Physical activity was encouraged but not assessed.
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? 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? No
  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? No
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