Orlistat over two years: weight loss and regain in a European trial

Why this study matters

Orlistat was one of the first medicines approved for long-term weight management. It works in the gut by blocking an enzyme that digests fat, so some of the fat in food passes through without being absorbed. This trial, published in 1998, was one of the main studies behind its use. It asked two questions that still matter today: how much weight is lost in the first year, and what happens to weight when the medicine is continued or stopped in the second year.

Who was in the study

The trial recruited 743 adults with obesity at 15 European centres. Their BMI, which is weight in kilograms divided by height in metres squared, was 28 to 47. After a four-week lead-in period, 688 people were randomized. The trial ran for two years after that, in two 52-week phases. The published summary does not report ages.

What the researchers did

Everyone began with a four-week single-blind lead-in on placebo and a slightly reduced-calorie diet with a 600 kcal per day deficit. Single-blind means participants did not know they were on placebo, but the researchers did. A placebo is an inactive capsule that looks like the medicine.

The 688 people who completed the lead-in were then randomized, meaning assigned by chance, to orlistat 120 mg three times a day or placebo for one year, with the same reduced-calorie diet. This part was double-blind: neither participants nor researchers knew who had the medicine.

In the second 52-week phase, people were reassigned to orlistat or placebo, again double-blind, with a weight-maintenance diet. Some people stayed on what they had, and some were switched. This design lets researchers compare continuing orlistat with stopping it, and starting orlistat with staying on placebo.

What they found

From the start of the lead-in to the end of year one, the orlistat group lost 10.2% of body weight (10.3 kg) and the placebo group lost 6.1% (6.1 kg). Because these figures count from the lead-in, they include weight lost before randomization. Counting only from randomization to the end of year one, the difference between groups was 3.9 kg, reported as a least-squares mean difference, which is an average adjusted for other factors. The summary does not give a confidence interval for this difference.

Total cholesterol, LDL cholesterol (often called "bad" cholesterol), the LDL-to-HDL ratio, blood sugar and insulin all fell more in the orlistat group than in the placebo group. The summary does not give the numbers.

Side effects and people who stopped

Gastrointestinal side effects, meaning effects on the gut such as oily stools, were more common in the orlistat group. Other symptoms occurred at a similar rate in both groups. The summary does not give percentages, and it does not report how many people in each group stopped the medicine or left the trial. The authors note that use beyond two years needs careful monitoring for both benefit and side effects.

What this study does not tell you

• The 10.2% and 6.1% figures include weight lost in the four-week lead-in before randomization. They are not the effect of the medicine alone.
• The second-year reassignment design is different from a simple two-year comparison. Results should not be read as two continuous years of treatment versus placebo.
• The trial is from the 1990s. Diet support and study methods have changed since then.
• The summary does not report how many people dropped out, which affects how confident we can be in the averages.
• These percentages cannot be compared with other medicine trials, which used different people, diets and time frames.
• The summary we reviewed does not state who funded the trial.

What it means in Canada

Orlistat has been available for many years, and this trial is part of the evidence behind it. The weight loss here reflects a medicine plus a supervised diet in a study setting. For information on this and other medicines, see the site's medicines pages, including semaglutide in Canada and tirzepatide in Canada. For coverage, see public drug coverage by province. To find weight-management services, see compare services.

Related reading

Other studies in this library that bear on the same question.

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