Diabetes drug 'may aid weight loss'
A “fat-busting jab could be the key to battling Britain’s obesity crisis”, the Daily Express has reported.
The news is based on a study looking at drugs called glucagon-like peptide-1 receptor (GLP-1R) agonists that can regulate blood sugar and suppress appetite. The drugs are currently used to control blood pressure in some diabetic patients, but this new study looked at whether the drugs could aid weight loss, both in people with diabetes and without. To examine the issue researchers combined the results of 25 previous studies involving GLP-1R drugs, looking at weight loss and other outcomes. The review found that those taking the drugs for at least 20 weeks lost an average of nearly 3kgs (7lb) more than those who were not on the drugs. Those on the drugs also had reductions in blood pressure and cholesterol levels.
There are two GLP-1R drugs currently licensed only for the treatment of type 2 diabetes that has not responded to other standard treatments. Whether or not the drugs can “cure” the “obesity crisis”, is not really a question for debate at the current time because they cannot be prescribed for people without type 2 diabetes, and even in people with type 2 diabetes they have very restricted eligibility criteria. As an accompanying editorial points out, these are relatively new drugs and their long-term safety profile is unknown. Further research into the risks and benefits of these drugs – both in people with diabetes and without – is required before they could be considered to be a possible treatment for weight loss in the wider population.
Where did the story come from?
The study was carried out by researchers from the University of Copenhagen. Although the review itself received no external funding, all the previous trials it included were funded by the pharmaceutical industry. Industry-funded studies are sometimes thought to report more positive findings.
The study was published in the peer-reviewed British Medical Journal.
The claims that the drugs could “cure” the obesity crisis, highlighted in both the Daily Mail and the Daily Express, are unduly optimistic, and do not take into account the fact that these drugs are currently licensed only for the treatment of type 2 diabetes that has not responded to standard treatments. They are not prescribed as weight loss drugs and not approved for the purposes of weight loss at present. Further research into the risks and benefits of these drugs is required before they could be considered to be weight loss treatments for wider population groups.
However, both the Mail and the Express did include comments from the BMJ’s editorial advocating further investigation into risks and benefits. The Express also pointed out common side effects, including nausea and diarrhoea.
What kind of research was this?
This was a systematic review and meta-analysis that looked at whether treatment with GLP-1R agonists resulted in weight loss in overweight or obese patients, with or without type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is a hormone secreted by the intestine in response to eating a meal to help regulate blood glucose levels. It has also been found to suppress appetite.
GLP-1R drugs are a relatively new treatment for people with type 2 diabetes. They work by binding to the surface of cells in the pancreas, increasing their secretion of insulin (which lowers blood glucose) and suppressing their release of a hormone called glucagon (which would increase blood glucose). Recent trials in patients with diabetes have also suggested they could result in weight loss. The two GLP-1R agonists, exenatide and liraglutide, are both administered by subcutaneous injection, and have a restricted licence for people with type 2 diabetes.
The authors point out that almost 3 million adults die each year as a result of being overweight or obese, and that additional methods to support weight loss would be valuable. For most people weight loss is difficult both to achieve and maintain, whether through diet or current weight loss medication.
What did the research involve?
The authors’ main aim was to assess the effects of GLP-1R agonists on the weight of overweight patients with or without type 2 diabetes, compared with placebo, no treatment or other anti-diabetic drugs. They also looked at other potential effects of the drugs, such as changes in blood pressure, liver enzymes, cholesterol and possible side effects. For those with type 2 diabetes they also looked at the effect of the drugs on blood sugar control.
The researchers based their review on a written protocol from the Cochrane Collaboration, which is an independent organisation that carries out systematic reviews. They carried out both electronic searches of medical databases, and manual searches, to identify all relevant trials. To be eligible for inclusion in the review studies had to meet certain criteria, including being randomised controlled trials rather than observational studies. They also had to involve adult patients who had a BMI of 25 or more and to have a trial duration of at least 20 weeks.
The GLP-1R agonists assessed were exenatide, given either twice a day or once a week, and liraglutide, given once a day.
The researchers examined the methods of randomisation used by the trials to find out if there was any risk of bias. For example, they looked at how patients were allocated to different groups in a trial and whether the methods used were adequate. They also looked at other measures of quality, including whether patients and researchers were adequately “blinded” to which treatment group patients were in, the number of patients who dropped out of the trial and why, and whether the trial retained the predefined numbers of participants who would be required for a meaningful analysis of the trial.
Once they had selected studies for inclusion, they used validated statistical methods to analyse the effects of the drugs on weight and other outcomes, compared to placebo, other interventions or no treatment. They carried out different types of analyses to confirm their results.
What were the basic results?
The researchers included 25 trials in their analysis. They found patients taking GLP-1R agonists achieved a greater weight loss than control groups:
- Overall, patients on the drugs lost on average 2.9kg more than those in control groups (95% confidence interval -3.6kg to -2.2kg loss; 21 trials, 6,411 participants).
- When looking separately at people with and without diabetes, they found that patients without diabetes lost on average 3.2kg more than patients in control groups (95% confidence interval -4.3kg to -2.1kg loss; three trials).
- Patients with diabetes lost on average 2.8kg more than diabetic patients in control groups (95% confidence interval -3.4kg to -2.3kg loss; 18 trials).
- The drugs also lowered blood pressure and cholesterol more than in the control groups, but had no effect on blood levels of certain liver enzymes.
- The drugs were associated with nausea, diarrhoea and vomiting, but no major episodes of hypoglycaemia (low blood sugar). Side effects did not appear to lead to higher drop-out rates among people taking GLP-1R agonists.
The researchers also reported on the quality of the methods and design of the trials. There was some difference between the design and results of the individual trials (heterogeneity), but no evidence of publication bias (which is where only trials with positive results are published).
How did the researchers interpret the results?
The researchers say their review provides evidence that GLP-1R agonists lead to weight loss in obese or overweight patients, irrespective of whether or not they have type 2 diabetes. They argue that the drugs should be considered in obese or overweight patients with diabetes, but stress that more research is needed on their effects in obese patients without diabetes.
This was a large, well-conducted systematic review that combined the results of trials investigating whether glucagon-like peptide-1 receptor (GLP-1R) agonists produce weight loss in overweight or obese people with or without type 2 diabetes. As the researchers described, a particular strength of their review was that they were able to obtain additional data on weight loss and other outcomes that had not been included in the original trial publications. They say that since outcomes are less likely to be described if they are less significant, this reduces the risk of reporting bias.
The review found that GLP-1R agonists were associated with weight loss in both people with and without diabetes. However, it is most important to note that these drugs are currently licensed only for the purposes of controlling blood sugar in people with type 2 diabetes that has not responded to other standard treatments. They cannot be prescribed for people without type 2 diabetes, and even in people with type 2 diabetes they have very restricted eligibility criteria.
Additional points worth noting:
- All the trials included received industry funding. Pharmaceutically funded trials have been found to lead to “more positive” conclusions, although the authors of this independent review say they carried out rigorous assessments of trial quality and none of their analyses revealed evidence of bias within these trials.
- There was some heterogeneity between trials. This means they used different methods and designs, which makes combining the results less reliable. However, the authors say they carried our further analyses that indicated this did not affect the results.
- The effect on weight was modest, leading to an additional weight loss of around 3kg (less than half a stone).
- Only three of the trials had assessed people without diabetes.
- The drugs are relatively new and their safety profile is still being discovered.
In conclusion, as an accompanying editorial points out, further trials are needed to investigate the benefits as well as the risks of these new drugs – both in people with diabetes and without – before they could be considered as possible treatments for weight loss in wider population groups.
- Vilsbøll T, Christensen M, Junker AE et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012; 344
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