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One Year Study Showed a 36% Loss in Excess Body Weight

May 25, 2012

Obese individuals completed a 1-year study and lost a mean 35.6% of excess body weight taking…. 

Patients taking 3 mg of liraglutide daily lost a mean 35.6% of body weight.Nick Finer, MBBS, consultant endocrinologist and bariatric physician at University College London Hospitals (UCLH) and UCLH Centre for Weight Loss, Metabolic and Endocrine Surgery at University College London, United Kingdom, reported that, the number needed to treat (NNT) to achieve a loss of 10% of total body weight was only 3 mg.

Dr. Finer described a 20-week trial extended to 52 weeks in which participants with a body mass index (BMI) of 30 to 40 kg/m2, aged 18-65 years, and with a fasting plasma glucose level less than 7.0 mmol/L (126 mg/dL) underwent a placebo run-in for 2 weeks and were then randomly assigned to 1 of 6 treatment groups: subcutaneous liraglutide at 1.2 mg/day, 1.8 mg/day, 2.4 mg/day, or 3.0 mg/day; subcutaneous placebo injection; or oral orlistat, 120 mg 3 times per day.

From weeks 20 to 52, the investigators and participants were blinded to liraglutide or placebo treatment. Throughout the trial, participants were on a diet providing a 500-kcal/day deficit and had increased physical activity.

In a post hoc analysis, the investigators explored the percentage of weight loss at 52 weeks in responders who achieved a 5% or greater weight loss at 12 weeks, as well as the percentage of excess body weight loss (EBWL) at 52 weeks with liraglutide.

All the groups (n = 90-98 per group) were well matched for baseline characteristics and differed little at baseline for individuals who completed 52 weeks. They were about 1 quarter male, aged 45 to 47 years, with body weight of 96.0 to 98.4 kg, BMI of 34.1 to 35.0 kg/m2, and excess body weight of 34.8 to 38.4 kg. Excess body weight is that amount in excess of having a calculated BMI of 25 kg/m2.

Across all the groups, a total of 356 participants completed 52 weeks.

Weight loss at 20 weeks continued out to 52 weeks in a dose-dependent manner for liraglutide. "You can see that orlistat patients did lose weight but were about equivalent to the lowest dose, the 1.2 mg of liraglutide, and about half that seen for the higher doses of liraglutide," Dr. Finer reported.

Patients who achieved at least a 5% weight loss at 12 weeks were considered responders, and that included 75% of people receiving 3.0 mg of liraglutide per day and 32% of those receiving placebo. The placebo responder group lost 7.1 kg by 52 weeks.

The highest-dose liraglutide nonresponders had lost only 3.4 kg at 12 weeks "but in fact continued to lose weight out to 1 year — 6 kilos — so one might argue these were not truly non-responders," Dr. Finer said.

Liraglutide responders had lost 7.9 kg at 12 weeks and by 52 weeks had lost 11.1 kg, which was a total body weight loss of nearly 12%.

Only 38% of the orlistat group were responders. "In terms of the ultimate weight loss in the responders’ group, there was not a large difference between orlistat and liraglutide," D. Finer said. "If you did respond to orlistat, you did well. It was just you were much less likely to respond."

Increasing liraglutide doses were associated with increasing amounts of EBWL; a 35.6% EBWL was seen with the 3.0-mg dose, which is the dose being carried forward in further weight loss trials.

No one who completed 52 weeks of treatment with liraglutide, 3.0 mg, gained weight, but 27% of those receiving placebo and 13% of those taking orlistat did.

"I would like to emphasize that liraglutide is not licensed as a weight loss agent at this stage and has not completed its safety trials let alone its long-term efficacy trials in phase 3 trials," Dr. Finer cautioned the audience.

In an intention-to-treat analysis, the NNT to achieve a 5% weight loss at 1 year was 2 for liraglutide, 3.0 mg; 3 for orlistat; and 4 for placebo. To achieve a 10% weight loss, the NNTs were 3, 7, and 10, respectively. "I think that we should be encouraged by these data," Dr. Finer said. "I think there’s often a lot of negativity, but an NNT of 3 [for liraglutide] for a 5% weight loss is really quite impressive."

Dr. Finer said the 35% EBWL with liraglutide stacks up favorably against the findings seen with bariatric surgery. "The use of excess body weight loss and also, I should say, numbers needed to treat, I think give clearly defined weight loss targets and perhaps a more optimistic interpretation of these data," he concluded.

Luca Busetto, MD, from the Department of Medical and Surgical Sciences and a member of the Obesity Center at the University of Padova in Padova, Italy, commented that newer, effective antiobesity drugs may in the future be the most appropriate treatment for people with class 1 obesity.

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"Probably the potency of these new drugs will be sufficient enough in order to solve the problem," he said. "So I think that we will not need surgery any more in patients with BMI between 30 to 35 [kg/m2], and probably also in the BMI class 35 to 40 [kg/m2] we may have some competition between drugs and surgery, at least less invasive surgery." For larger patients, Dr. Busetto thinks that surgery will remain the most efficacious therapy for at least the next 5 to 10 years.

For patients who can be managed with drugs, he thinks therapy will probably have to be life-long, although long-term data are lacking. "Obesity is a chronic disease, and probably we need to think of treating obesity as we treat hypertension, as we treat type 2 diabetes," Dr. Busetto said.

But as with other chronic medications, adherence may be a problem, especially with an injectable drug such as liraglutide, although development of longer-acting GLP-1 analogues that require less frequent injections may help.

Dr. Busetto predicted that liraglutide for weight loss may face some regulatory hurdles both in the United States and in Europe because licensing agencies may require not only demonstration of efficacy for weight loss but also demonstration of cardiovascular safety, "probably as a consequence of the problem with sibutramine in the past."

Dr. Finer has been an advisory board member and done paid lecturing and commercially sponsored research for Novo Nordisk A/S. He has also received lecture and consultancy fees from Roche in the past. The study was funded by Novo Nordisk A/S. Dr. Busetto has disclosed no relevant financial relationships.

19th European Congress on Obesity (ECO). Abstract #152. Presented May 11, 2012.