EAL

Weight Management

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To report the 4-year follow-up of patients with respect to weight and glycemic control.

Inclusion Criteria:

Insulin-dependent and non-insulin dependent diabetic males and females
Aged 16-70 years
BMI 28-45 kg/m²

Exclusion Criteria:

Any patient who has lost more than 3 kg in weight in the previous year
Pregnant women
Known psychiatric disorders
Patients on oral corticosteroids

Description of Study Protocol:

Recruitment

Possible subjects were contacted via mail and asked to reply using a stamped addressed envelope.

Design

Subjects were randomized into one of the four 1-year treatment groups:

Individual dietetic consultation on 6 weekly intervals for the first 6 months and then 2 monthly for the remainder of the year
Behavioral therapy involving a physiotherapist and clinical psychologist as well as a dietitian in groups bi-weekly for 3 months and then 2 month intervals for the remainder of the year.
Individual dietetic consultations at 6 weekly intervals for the first 6 months and then 2 monthly for the remainder of the year with the addition of dexfenfluramine 15mg twice per day for the first 3 months
Individual dietetic consultation combining home and clinic visits. Home visit group at 6 weekly intervals for the first 6 months and then 2 monthly for the remainder of the year. The initial and the fourth visits were at the patient's home and the others were in the clinic.

A further 58 patients were randomly selected to reflect the routine diabetic service during the initial 1 year study period.

Blinding used (if applicable): Not applicable

Intervention (if applicable)

All patients were seen by the same dietitian and individual energy prescriptions were based on 50-55% of total energy from carbohydrates, 30-35% from fat and 10-15% from protein.

Statistical Analysis

The data for the four treatment groups were analyzed in two ways: on an 'intent to treat' from the outset and on a 'completion' basis for those who completed the planned treatment regimen at 1 year. Comparision was not made statistically on a completion basis.

Unpaired and paired t tests, quartile, chi-square and two way ANOVA were used to compare the data. Mean and 95% confidence intervals are given.

Data Collection Summary:

Timing of Measurements

at 1 year
at 4 years

Dependent Variables

Weight change at 1 year and 4 year follow-up (kg)
Weight loss of 3 kg or greater
Quartiles for weight change (kg) on an intent to treat basis
HbA_1C measured in both 'intent to treat' and 'completion' groups at outset and year 4.

Independent Variables

Intervention method:

Behavioral
Dexfenfluramine
Home visit
Routine

Control Variables

Clinic visit group

Description of Actual Data Sample:

Initial N: 409 were selected at random and invited to participate. 147 randomized into regimens.

Attrition (final N): 132 available for study. 9 had died and 6 had become non-attenders.

Age: (in years) Clinic visit: 53.3, Behavioral: 58.2, Dexfenfluramine: 54.5, Home visits: 55, Routine: 53.3

Ethnicity: data not provided

Other relevant demographics: Male:Female ratio, IDDM vs NIDDM

Anthropometrics: BMI (kg/m²), weight change at 1 year (kg), weight change at 4 year (kg)

Location: Diabetes Center, Ninewells Hospital, UK.

Summary of Results:

Other Findings

Intent to Treat Analysis:

Only the dexfenfluramine group showed a significant weight loss after 4 years (p= 0.025). Within this group, the mean weight loss of the females at year 4 was 4.86kg (p= 0.001).
Within the clinic visit group, the males showed a significant gain in weight (mean +2.93kg, p= 0.005), the females an insignificant loss (-1.61 kg, p= 0.08).
No difference in the weight change at year 4 within any of the four groups when analyzed for treatment at the outset-namely insulin or non-insulin treatment.
The weight loss of the dexfenfluramine group was significantly greater at year 4 compared to both the clinic visit group (p= <0.05) and the cohort patients (p= <0.05).

Completion Analysis:

No significant weight loss over 4 years and there were no significant weight differences between the two groups.
In the dexfenfluramine group the females showed a mean loss of 4.73kg (p= 0.005), but the males gained overall 1.62kg.
In the clinic visit group, the females showed a mean loss 2.69 kg (p = 0.03) whereas the males gained 2.2kg (p=0.05).

Weight Loss of 3 kg or Greater:

More patients in the dexfenfluramine group lost 3kg or greater than the clinic visit group (p= <0.02).
Achievement of this goal at year 4 was significantly greater in the home visit (p= <0.05), but not the behavioral group when compared to the clinic visit group.

Quartile Analysis:

The most weight loss across the mid range centiles was in the dexfenfluramine group.

HbA_1C:

No significant changes in HbA_1C in any of the groups comparing outset with year 4 values.

Author Conclusion:

Although now withdrawn, the use of an appetite suppressant dexfenfluramine for just 3 months would appear to have a long-term advantage on weight loss in this diabetic population, although the weight loss was not associated with an improvement in glycemic control.

Funding Source:

Industry:

Servier Laboratories

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

The dexfenfluramine group showed the best weight loss results, however overall diappointing results given the fact that this drug is no longer approved for use and that there was no improvement in glycemic control.

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)	No
	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)	No

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?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	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?	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
	7.1.	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)?	???
	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