• Aged 18 years old or older
• Body mass index 30kg/m² or more
• No diabetes diagnosis
• Able to lose 2.5kg or more during a four-week lead-in period.

Recruitment

Data were pooled from five clinical trials.

Design

During a four-week single-blind lead-in period, patients received a low-calorie diet, and those who successfully lost 2.5kg or more were then randomized to 12 months double-blind treatment with either orlistat 120mg up to three times per day plus low-calorie diet or to placebo plus low-calorie diet. The low-calorie diet was designed to induce a 2,090kJ daily energy deficit containing 30% of energy as fat. In month three, patients were only to continue on medication only if they achieved 5% or more weight loss from baseline. Patients who achieved this weight loss continued on medication for a total of 12 months, while those who did not stopped taking medication but were assumed to continue with the diet as the only option for the remaining nine months. For this group the authors assumed the same 12 months' weight loss as for patients in the placebo arm who lost less than 5% weight after three months. For sensitivity analyses, the authors assumed all non-responding Orlistat patients were also withdrawn from diet only at month three. Patients were assumed to reach maximum weight loss in month 12. For base-case estimate, Orlistat plus diet was compared with a diet-only treatment regimen. For patients on diet only, all were assumed to continue to be on a diet for 12 months irrespective of achieving 5% weight loss at three months. For analysis, all patient data were included up to month 12 or to point of withdrawal. For base-case estimation a consumption of 2.3 capsules of Orlistat per day was assumed, although adherence was not measured. For base-case calculations, the authors assumed all patients remained on a diet throughout the 12 month period unless they withdrew altogether, as well as assuming the same number of outpatient physician and dietitian visits (four each) for both the orlistat and diet-only treatment arms. However, physician and dietitian visit costs are absent in the no-diet alternative estimated in the sensitivity analyses. Patients withdrawing from the orlistat arm had initial drug costs needing to be included, assumed to be equal to three months' prescription. The authors also used a cost-utility analysis to include improvements in quality of life, presented as an incremental cost per additional QALY (quality-adjusted life years) gained. Healthcare costs (per the Swedish healthcare system) related to visits to doctors and dietitians for the dietary program, 12-month costs for Orlistat (at 2003 prices) and costs for controlling and treating patients with type 2 diabetes for up to 10 years were included in the estimates. In the sensitivity analyses the authors also included a no-diet treatment alternative; it was assumed that in this group patients remained at the same BMI level throughout the study period. In addition the authors calculated the impact on the cost-effectiveness estimation if temporary weight loss had no effect on diabetes incidence. 

Blinding Used
Patients were randomized to a 12-month double-blind treatment.

Intervention

Patients were randomized to receive either orlistat 120mg up to three times per day plus low-calorie diet or to placebo plus low-calorie diet.

Statistical Analysis

Results were calculated by means of Monte Carlo simulation in order to estimate uncertainty around the costs and effects estimations. A probabilistic sensitivity analysis was estimated using available stochastic information for some of the parameters. The distribution of the cost-effectiveness ratios was estimated using the net benefit approach. The robustness of the results was also tested in univariate sensitivity analyses by changing parameter values for some of the deterministic variables. In the base-case analysis, a 3% discount rate was used on both costs and effects and the impact of using 0% and 5% in a sensitivity analysis was tested. 

Timing of Measurements

Patient weight was reported at baseline, three months and 12 months.

Dependent Variables

• Weight change
• Health benefit of temporary weight change (measured in the number of QALYs gained)
• Incidence of type 2 diabetes.

Independent Variables

Patients were randomized to either orlistat plus diet or diet-only treatment arms.

Control Variables

Both treatment groups were compared with a no-diet alternative arm. 

• Initial N: N=1,386 patients
• Anthropometrics: The average patient in the orlistat plus diet arm had an initial BMI of 36.4kg/m² and 36.2kg/m² in the diet-only arm
• Location: Five pivotal clinical trials were pooled; two from the United States and three primarily from Europe.

Key Findings

• In the pooled analysis, 49% of all patients starting on orlistat achieved 5% or more weight loss after three months of active treatment, compared with only 26.3% of patients randomized to diet only
• At 12 months, weight loss was significantly lower in the orlistat arm (11.6%) compared with the placebo arm (7.9%)
• A total of 10% or more weight loss from initial weight at 12 months was 44.8% in the orlistat arm compared with 24.5% in the diet only arm
• The average added cost per patient was €399 starting on orlistat (€720) compared with a patient starting on diet only (€320) (based upon 2003 costs)
• The expected QALY gain per patient starting on diet and orlistat was 0.122 compared to 0.0915 for diet alone
• For orlistat responders, the QALY gain was estimated to be 0.45 QALY gain after 12 months' treatment. The incremental cost per QALY gained for a patient starting on orlistat (including responders and non-responders) was estimated to be €13,125.

• QALY: Quality-adjusted life years
• The study authors did not report any P-values for results
• The study authors did not detail the role of the dietitian in the intervention, only mentioning the estimated cost of four visits over the 12-month intervention period.