EAL

DM: Weight Management (2007)

Citation:

Sanchez-Reyes L, Fanghanel G, Yamamoto J, Martinez-Rivas L, Campos-Franco E, Berber A. Use of sibutramine in overweight adult Hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind placebo-controlled clinical trial. Clinical Therapeutics 2004; 26(9):1427-1435.

PubMed ID: 15531005

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

The purpose was to assess the effect of sibutramine combined with glibenclamide on the effect of body weight and glycemic control in obese Hispanic patients with type 2 diabetes.

Inclusion Criteria:

adult ages 24 to 65
overweight or obese (BMI > 27 kg/m²)
diagnosis with type 2 diabetes with stable fasting plasma glucose levels (<140 mg/dL)
receiving glibenclamide (Glyburide) for at least 2 weeks
gave informed consent

Exclusion Criteria:

endocrine diseases other than type 2 diabetes
uncontrolled hypertension (blood pressure > 140/90 mm Hg)
autoimmune disease
ischemic heart disease
arrhythmia
psychosis
patients requiring medications acting on the central nervous system, cathartics, thyroid hormone replacement or diuretics
pregnant or lactating women

Description of Study Protocol:

Recruitment: patients lived in the Mexico City area

Design: 12-month double-blind, placebo-controlled randomized clinical trial

Blinding used: double blind

Intervention: treatment group received 10 mg sibutramine daily

Statistical Analysis

last observation carried forward methodology used in case of missing data
paired comparisons assessed using Student t test for continuous variables and Wilcoxon signed rank test for ordinal variables
multivariate analysis of variance (MANOVA)
significance set at 5% level for all tests

Data Collection Summary:

Timing of Measurements

anthropometrics (height, weight, waist circumference) and fasting glucose measured monthly
HbA1c determined at baseline, 6 and 12 months
electrocardiogram and standard laboratory tests (hematology, blood chemistry, urinalysis, plasma glucose, serum lipid levels) at baseline and end of study

Dependent Variables

body weight (kg) and body mass index (kg/m²)
waist circumference
plasma fasting glucose

Independent Variables

sibutramine treatment (10 mg per day) or placebo

Control Variables

all subjects were treated with glibenclamide

Description of Actual Data Sample:

Initial N: 86

sibutramine plus glibenclamide: 44 (28 females/16 males)
glibenclamide: 42 (31 females/11 males)

Attrition: 47 subjects completed study (45% attrition)

sibutramine plus glibenclamide: 24 completed study (45% attrition)
glibenclamide: 23 completed study (45% attrition)

Age: adults age range 24-65; sibutramine group mean 47.6 ± 9.0 years; placebo group mean 45.8 ± 8.1 years

Ethnicity: Hispanic (Mexican)

Anthropometrics:

No significant differences between treatment and control groups in gender, age, body weight, BMI, waist circumference, waist-to-hip ratio, blood pressure, heart rate, fasting glucose, duration of diet or previous treatment with diet and sulfonylurea drugs.

Location: General Hospital of Mexico, Mexico City

Summary of Results:

Compliance with drug intake was 90% for as long as patients remained in the trial.

Variables (Change after 12 months)	Sibutramine Group Measures (statistical significance of difference from baseline to 12 mo)	Control group Measures (statistical significance of difference from baseline to 12 mo)	Statistical significance difference between groups
weight (kg)	- 4.1 kg (P<0.001)	- 1.4 kg/m²	P<0.05
Body Mass Index (kg/m²)	- 1.7% (P<0.001)	- 0.6 kg/m²(P<0.05)	P<0.05
waist circumference (cm)	- 4.1 cm (P<0.001)	- 1.3 cm (P<0.05)	P<0.05
plasma fasting glucose	- 26.2 mg/dL (P<0.001)	- 18.8 mg/dL (P<0.05)	not significant
HgA_1c	-0.6% (P<0.001)	0.1% (NS)	P<0.05
5% responders*	59.1% (26/44)	16.7% (7/42)	P<0.05
10% responders*	25% (11/44)	4.8% (2/42)	P<0.05

* the authors did not define "responders" (likely meaning is patients who lost 5% or 10% of body weight in the 12 month period)

Other Findings

Fat mass: patients who received sibutraine had significant loss in mean fat mass (P<0.05); there was no significant fat loss in patients receiving placebo.
Blood pressure: both groups had small but significant decreases
- 5 patients in sibutramine group and 4 in placebo group had clinically significant increases in blood pressure (>150/110 mmHg)
Reduction in dosage of glibenclamide (no significant differences between treatment and placebo groups)
- sibutramine group: mean dose reduced from 13.7 to 7.8 mg by month 12 (P<0.001) and 7 patients required no glibenclamide treatment
- placebo group: glibenclamide dose reduced from 14.0 to 11.2 (P<0.05) and 5 patients required no treatments

Author Conclusion:

Sibutramine combined with glibenclamide therapy was associated with better weight loss glycemic control than glibenclmide alone.

Funding Source:

Industry:

Abbott Labs

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

General Hospital of Mexico

Reviewer Comments:

Trade name of glibenclamide is Glyburide. More than 40% of the subjects had received sulfonylurea drugs prior to the trial. Although this paper qualifies for a positive quality rating, note that the trial had a 45% drop out rate and there were no intent-to-treat analyses.

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	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
	2.1.	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
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	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
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	3.	Were study groups comparable?	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
	3.1.	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
	3.2.	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
	3.3.	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
	3.4.	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
	3.5.	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
	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.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	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
	4.2.	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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	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
	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.	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
	5.1.	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
	5.2.	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
	5.3.	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
	5.4.	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
	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.	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
	6.1.	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
	6.2.	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
	6.3.	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
	6.4.	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
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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
	8.3.	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)?	No
	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	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
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	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.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes