“Patients given a new anti-obesity drug lost more than a stone in weight in five months,” said The Times . The injectable drug, liraglutide, was reported as being almost twice as effective as other treatments in the study.
The Daily Mail wrongly reports that the drug has been licensed for use in obese patients in the UK since July.
In this high-quality trial, 564 obese or severely obese patients were injected with one of four different doses of liraglutide a day, or were given a daily 'dummy' jab or orlistat pills three times a day. All patients followed a calorie-restricted diet and increased their physical activity.
Contrary to some newspaper reports, this drug in is only licensed to treat type 2 diabetes in tablet form in Europe, and is not yet licensed in the US. Average weight loss on the highest dose of liraglutide was more than 7.2 kg at 20 weeks, which was 4.4 kg more than placebo.
This was significantly more than the weight loss achieved on orlistat and it was clinically important.
The researchers acknowledge that the long-term effects of the injection and its safety will need to be understood if the licence for this drug is extended from type 2 diabetes to obesity.
Where did the story come from?
This research was carried out by Professor Arne Astrup and colleagues from the University of Copenhagen in Denmark and other universities in Europe. It was funded by Novo Nordisk A/S, the Danish manufacturers of the drug. The study was published in the peer-reviewed medical journal The Lancet .
What kind of scientific study was this?
This was a randomised controlled trial that was double blind and placebo-controlled in part. The researchers stress the importance of weight loss research by highlighting the fact that obesity has risen dramatically in recent years, but there are only a few safe and effective drugs currently available.
The researchers explain that liraglutide was developed for the treatment of type 2 diabetes. It improves blood sugar control and blood pressure when taken in doses of up to 1.8 mg a day. As the patients in those trials also lost weight, the researchers wanted to see if the drug could be used to treat obesity.
Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue, one of a group of drugs that are similar to hormones released by the gut. They act by increasing the amount of insulin released from the pancreas after eating, before blood glucose levels rise. In its natural form, GLP-1 is metabolised quickly within an hour, and is therefore not very useful as a therapeutic agent. However, injected forms can last longer. Liraglutide has been developed so that it is suitable for once-daily injection.
The researchers screened 733 adults for inclusion in the trial. Some were excluded for various reasons, including having known type 1 or 2 diabetes mellitus or other major medical conditions, being obese as a result of drug treatment, or having already been treated by surgery. An additional 52 people were excluded during a two-week preparation period (run-in phase).
This left 564 individuals with a body mass index of 30-40 kg/m² and aged between 18 and 65. These patients were randomly assigned to one of four liraglutide doses (administered once a day by injection under the skin) or two alternative controls:
- 95 patients received 1.2 mg liraglutide,
- 90 received 1.8 mg liraglutide,
- 93 received 2.4 mg liraglutide,
- 93 received 3.0 mg liraglutide,
- 98 received a placebo injection, and
- 95 received orlistat 120 mg three times a day by mouth.
All individuals were put on an energy-deficit diet, where they received 500 fewer calories a day than they needed, and increased their physical activity throughout the trial, including the two-week run-in.
Weight change was the main outcome of interest. After analysis at 20 weeks, all the participants could then enrol in an 84-week open-label extension period, in which they knew which treatment they were receiving.
What were the results of the study?
The participants who took liraglutide at all four doses lost significantly more weight than those on placebo or orlistat.
The mean (average) weight loss for each group was:
- 4.8 kg for participants on 1.2 mg liragluti,
- 5.5 kg on 1.8 mg liraglutide,
- 6.3 kg on 2.4 mg liraglutide,
- 7.2 kg on 3.0 mg liraglutide,
- 2.8 kg with placebo, and
- 4.1 kg with orlistat.
Weight loss with liraglutide was 2.1 kg (95% CI 0.6-3.6) to 4.4 kg (2.9-6.0) greater than the weight lost with the placebo.
In the group taking 3.0 mg liraglutide, 70 patients (76%) lost more than 5% of their weight. In the placebo group, 29 participants (30%) lost more than 5% of their weight. In the orlistat group, 42 (44%) lost more than 5% of their body weight.
Side effects included nausea and vomiting, which occurred more often in patients on liraglutide than those on placebo, and were highest among the 3.0 mg group. The researchers say that the adverse events were mainly temporary and rarely led to treatment being discontinued.
The researchers also report that blood pressure and the prevalence of pre-diabetes was reduced. Pre-diabetes was defined as either impaired fasting plasma glucose or glucose tolerance, which were measured during a separate two-hour blood test called the OGTT at the beginning of the study and at week 20.
What interpretations did the researchers draw from these results?
The researchers say that liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces pre-diabetes.
What does the NHS Knowledge Service make of this study?
This well-conducted study has confirmed the efficacy of liraglutide and showed a dose response, i.e. higher doses of the drug are associated with larger responses, benefits and harms. There are a few points to note:
- The average reduction in weight might seem small, but the change compared to placebo and the next best alternative (orlistat) was clinically important and statistically significant.
- The accompanying improvement in risk factors, blood pressure and glucose measurements is also encouraging.
- The dose of liraglutide used in this trial is higher than the dose approved for use in diabetes. The researchers say that phase 3 studies with liraglutide at this dose (3.0 mg) are currently planned or underway.
This trial provides promising results, but the drug still needs to be approved for this use. There may be safety risks with taking a daily injection of the drug long term. Finally, the long-term risk-benefit profile for liraglutide as well as its weight maintenance capabilities were not investigated in this trial.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Mail, 23 October 2009
The Times, 23 October 2009
The Daily Telegraph, 23 October 2009
Links to the science
The Lancet, early online publication, October 23 2009
Cochrane Database of Systematic Reviews 2003, Issue 4
JAMA 2007; 298(2): 194-206