Redmon JB, Reck KP, Raatz SK, Swanson JE, Kwong CA, Ji H, Thomas W, Bantle JP. Two-year outcome of a combination of weight loss therapies for Type 2 diabetes. Diabetes Care 2005;28:1311-1315.PubMed ID: 15920044
- 30-70 years
- diagnosis of type 2 diabetes with HbA1c between 7.0 and 10.0%
- BMI between 27 and 50kg/m2
- stable weight for the previous 3 months
- constant doses of any diabetes, hypertension, and lipid medications for at least 1 month
- current use or use in the previous 6 months of insulin
- prior use of sibutramine
- use of any weight loss product or participation in any formal weight loss program in the previous month
- significant abnormality on screening tests
- history of heart disease or stroke
- prior bariatric surgery
- lactose intolerance
- any chronic disease or therapy that would make adherence to the study protocol difficult
Design: randomized controlled trial
Blinding used (if applicable): Implied for laboratory measures.
Intervention (if applicable)
- Randomization was stratified by sex.
- Standard/Combination (S/C) Therapy: Subjects in both groups received individual counseling by a registered dietitian. At baseline, each subject's basal energy requirement was calculated and resting energy expenditure was measured. Using these data and an estimate of the subject's typical activity level, the dietitian prescribed an individualized diet that would promote a 500- to 1,000-kcal reduction in daily energy intake. Subjects also received an individualized exercise prescription that included, at a minimum, walking for 30 minutes three times weekly added to usual activity. All subjects received an educational program of dietary, exericse, and behavioral strategies to facilitate weight loss using a commercially available dietary and lifestyle modification resource. After 1 year on standard therapy, this group was crossed over to combination therapy for the 2nd year of the study.
- Combination (C) Therapy: In addition to the standard therapy program described, the combination therapy weight loss program consisted of the following interventions: 1) 10 mg sibutramine daily with the option to increase to 15 mg daily after 6 months if BMI remained >/=27 kg/m2; 2) low-calorie diets providing 900-1,300 kcal per day made up exclusively of meal replacement products (meal shakes or meal bars, 220 kcal/serving, four to six servings daily) for 7 consecutive days every 2 months; and 3) between low-calorie-diet weeks, use of one meal replacement product and one snack bar daily (120 kcal/snack bar) to replace one usual meal and snack and thereby facilitate achievement of the goal of a 500- to 1,000-kcal/day reduction in energy intake. Meal replacement products and snack bars were provided by Slim Fast Foods Company. Two years of continuous combination therapy.
- Diabetes, hypertension, and lipid medications were adjusted, added or stopped according to a pre-established protocol.
- All subjects were to attempt to achieve HbA1c values <7% through weight loss.
- Diabetes medication was initiated or increased if there were symptoms attributable to hyperglycemia or if HbA1c was >10.0%. Diabetes medication was reduced or discontinued if symptomatic hypoglycemia occurred more than two times per week or home blood glucose values were frequently <80 mg/dL.
- Cost of program was about $6 per day, from which the cost of usual meals and snacks that were omitted (two to six per day) should be substracted.
- Data from subjects who discontinued study participation before 24 months were excluded from the analysis.
- Changes from baseline to 24 months in study parameters were compared with a treatment group by a paired t test.
- A chi-square test was used to compare categorical data.
- Relationships between weight loss with C therapy and baseline parameters were examined by least squares linear regression.
Timing of Measurements
- Baseline and follow-up visits at 1 month, 2 months, and every 2 months thereafter. Subjects were also seen after each low-calorie-diet week for measurement of weight, pulse, and blood pressure.
- Blood samples for fasting glucose, lipids, and HbA1c were obtained at baseline and 2, 4, 6, 8, 10, 12, 16, 20, and 24 months.
- Body composition was assessed at baseline and at 2, 6, 12, 16, and 24 months.
- weight and change in weight: electronic scale with subjects wearing light clothing and no shoes
- height: stadiometer
- blood pressure and pulse: automated blood pressure cuff after subjects were seated for 5 min; three readings were obtained and the average of the last two was recorded
- fasting plasma glucose
- fasting plasma total cholesterol
- HDL cholesterol
- LDL cholesterol: calculated unless fasting plasma triglycerides exceeded 400 mg/dL
- body composition: total-body-dual energy X-ray absorptiometry using a Lunar Prodigy
- resting energy expenditure: measured using a DeltaTrac II Metabolic Monitor
- C therapy: combination therapy
- S/C therapy: standard therapy and then crossed over to combination therapy
Initial N: 61 were enrolled
Attrition (final N):
Two subjects in S/C group withdrew before their first follow-up visit
54 completed 1 year of the study (27 in each group)
48 completed 2 years of the study (23 in C therapy, 11 women and 12 men; 25 in S/C therapy)
Reasons for early study termination were inability to keep study visits (three subjects), desire to undergo bariatric surgery (one subject), desire to start a commercial weight loss program (two subjects), personal reasons (four subjects), and death as a passenger in a motor vehicle accident (one subject).
Age: only given for the C therapy group; 51 ± 2
Ethnicity: not given
Other relevant demographics: not given
data only given for C therapy group
See Table 1
Duration of diabetes (years): 4 ± 1
Subjects were evaluated in the University of Minnesota General Clinical Research Center.
Reviewers note: main interest of investigators was to assess the long-term effects of combination therapy in the C therapy group
Table 1 - comparison of baseline and 2-year data for subjects on C therapy
|Two or more||14||17|
|Weight (kg)||113.2 ± 4.4||108.6 ± 4.2||-4.6 ± 1.2||0.001|
|BMI (kg/m2)||38.5 ± 1.1||36.9 ± 1.0||-1.6 ± 0.4||0.001|
|Body fat (kg)||46.8 ± 2.5||44.8 ± 2.2||-2.0 ± 0.8||0.03|
|Lean body mass (kg)||62.6 ± 3.0||60.0 ± 2.9||-2.6 ± 0.8||0.002|
|Fasting glucose (mg/dL)||158 ± 9||148 ± 12||-9 ± 15||0.56|
|HbA1c||8.1 ± 0.2||7.6 ± 0.2||-0.5 ± 0.3||0.08|
|Resting pulse (bpm)||80 ± 2||79 ± 2||-1 ± 2||0.55|
|Systolic blood pressure (mmHg)||139 ± 2||132 ± 2||-7 ± 3||0.03|
|Diastolic blood pressure (mmHg)||77 ± 2||73 ± 2||-4 ± 2||0.06|
|Fasting cholesterol (mg/dL)||197 ± 10||185 ± 9||-12 ± 11||0.29|
|HDL cholesterol (mg/dL)||40 ± 2||38 ± 2||-1 ± 1||0.37|
|LDL cholesterol (mg/dL)*||115 ± 8||102 ± 6||-13 ± 9||0.14|
|Fasting triglycerides (mg/dL)||233 ± 32||225 ± 43||-8 ± 42||0.85|
*Excludes four subjects with fasting triglycerides >400 mg/dL at baseline.
- Mean weight loss was greatest at 10 months in the C therapy group followed by a slow regain over the subsequent 14 months.
- A pattern of weight loss during low-calorie-diet weeks with subsequent weight regain in the period between low-calorie-diet weeks was observed through-out the study.
- The S/C therapy group lost little weight during year 1 of standard therapy. After starting combination therapy at the beginning of year 2, this group demonstrated a pattern of weight loss similar to that observed during year 1 in the C therapy group. Weight loss in the S/C therapy group at 2 years was 8.1 ± 1.6 kg (P < 0.001).
- Baseline HbA1c was 8.1 ± 0.2% for both groups. HbA1c at 2 years decreased 0.5 ± 0.3 % in the C therapy group (P=0.08) and 0.3 ± 0.2 % in the S/C therapy group (P=0.18).
- Compliance with the intermittent low-calorie-diet weeks was generally good, as evidenced by the repetitive demonstration of weight loss during these weeks. During the 2nd year of the study, there was less weight loss during low-calorie-diet weeks and more weight gain during intervening weeks. This led to a gradual increase in weight during the 2nd year of the study.
- Women had significantly greater weight loss than men after 12 months of C therapy (8.6 ± 1.5 vs 4.7 ± 0.9%, P=0.03).
- Percent body fat at baseline was also significantly correlated with weight loss (r = 0.49, P=0.02). Women had significantly greater percent body fat than men, so sex and body fat are not independent of each other.
- After 2 years, 14 subjects (61%) in the C therapy group were taking sibutramine (15 mg daily in 13 subjects and 10 mg daily in one subject). Sibutramine was discontinued by nine subjects for a variety of reasons, which included starting antidepressant therapy (one subject), possible side effects (constipation, dry mouth, and difficulty with urination, one subject each), concern over possible blood pressure effects (three subjects), and personal reasons (two subjects).
- No serious adverse events related to the study protocol.
- Some subjects experienced mild hypoglycemia during low-calorie-diet weeks and required temporary reductions in diabetes medications.
The weight regain may have been due to decreased adherence to the combination therapy program, perhaps because the novelty of the program decreased over time.
Overweight or obese people with type 2 diabetes receiving a weight loss intervention that combined intermittent low-calorie diets, daily meal replacements, and the medication sibutramine achieved and maintained significant weight loss over a 2-year period. This was accompanied by improvement in diabetes control.
Limitations as given by authors:
THe long-term treatment effect of combination therapy would have been better assessed if we had an appropriate control group throughout the entire study. The S/C therapy group provided an appropriate control for the initial study year, but not the second due to crossover to combination therapy.
The crossover was done for retention purposes because the investigators felt it unlikely that subjects would remain active participants in standard therapy for 2 years.
Because of study design, it was not possible to determine which component of combination therapy was most important in producing and sustaining weight loss.
- One year results previously reported: Diabetes Care 26:2505-2511, 2003.
- Study design has problems as mentioned by the authors: unable to separate out effective component in C therapy; and, lack of an appropriate control for year 2.
- The changes in fasting glucose and HbA1c were not statistically significant in the C therapy group and HbA1c did not decrease below 7%.
- A possible conflict of interest exists as grants from Abbott Laboratories and Slim Fast Nutrition Institute supported the project.
Quality Criteria Checklist: Primary Research
|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|
|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?||???|
|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?||???|
|3.||Were study groups comparable?||No|
|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?||???|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||No|
|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?||???|
|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?||No|
|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?||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?||???|
|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?||???|
|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)?||No|
|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?||No|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||No|