US weight-loss drug lorcaserin 'safe' but only modes...

"A major study has found promising results for the safety of a weight-loss drug available in the US," BBC News reports.

This large, international, randomised controlled trial including 12,000 overweight and obese people, found that those who took a weight-loss drug called loriciferan lost 2.8kg more than those who took a placebo (dummy treatment) over a period of 40 months.

Some previous weight-loss drugs were found to increase the risk of cardiovascular disease, such as heart attacks or stroke, so were taken off the market. The purpose of this new study was to see that people taking lorcaserin were not facing a similar risk.

Researchers found that people taking lorcaserin were not placed at increased risk of heart attack or stroke, compared to people in the placebo group.

There is a catch. This drug is only available to prescribe in the US; it has not been approved in Europe and therefore the UK. It's also quite expensive, as it could cost around £155 to £225 per month, which equates to around £1,860 to £2,700 per year. So if lorcaserin does come to the UK market, there is no guarantee that it will be made available free of charge on the NHS.

Although this drug may seem like an easy option for weight loss, the participants in this study were supposed to take the drug alongside a diet and exercise plan.

Read more about losing weight safely with the NHS Weight Loss Plan.

Where did the story come from?

The study was carried out by a large group of researchers from several international institutions in Australia, the Bahamas, Canada, Chile, Mexico, New Zealand, Poland and the US. It was funded by the Japanese pharmaceutical company Eisai, which owns the rights to develop and market lorcaserin. The study was published in the peer-reviewed New England Journal of Medicine.

Not surprisingly, as this research presents what may initially appear to be a "quick fix" for weight loss, it was widely covered by the UK media. However, not all reporting of this study was accurate. The Mail Online for example, states the drug was shown to be safe "long term" but the study could only show the drug's safety for 40 months.

Many news sites describe the drug as a "Holy Grail" that can "help millions lose weight". In fact the drug was actually part of a combined treatment plan that also included dietary changes and exercise. So people should not expect to rely on the drug alone for weight loss.

Also, the results in terms of weight loss were modest. Most people taking the drug were still in the overweight or obese category by the end of the study.

What kind of research was this?

This study was a randomised controlled trial (RCT) that was double blinded, and placebo controlled. This means the risk of bias was minimised by ensuring the participants and the researchers were unaware whether they received treatment or placebo. These kinds of RCTs are the best trials for assessing the effect of an intervention and reducing the impact of confounders.

Lorcaserin is a drug used to regulate appetite and has been approved by the US Food and Drug Administration since 2012 to complement a reduced calorie diet and increased physical activity for long-term weight management. It is unlicensed in Europe.

What did the research involve?

The researchers recruited 12,000 overweight or obese patients from 473 different study sites in 8 countries between January 2014 and November 2015. The participants had to have a body mass index (BMI) of at least 27, with atherosclerotic cardiovascular disease (clogged arteries) or multiple cardiovascular risk factors such as diabetes and high blood pressure.

The participants were randomised to take lorcaserin 10mg twice daily or a placebo. All participants were also encouraged to participate in a standardised weight-management programme, consisting of intensive behaviour therapy that included dietary and exercise information. Participants also had unlimited access to a dietitian over the phone.

The primary outcome was major cardiovascular events, which comprised:

cardiovascular death
myocardial infarction (heart attack)
stroke
unstable angina
heart failure
coronary revascularisation (surgery to unblock heart vessels)

The researchers also wanted to see if taking lorcaserin was associated with any other health events, including:

any cancer
early breast cancer
lumps in the breast
euphoria – (an intense feeling of happiness)
psychosis
suicidal intentions
death by suicide
drug side effects such as an increased body temperature, agitation, sweating etc
a persistent erection

The researchers used statistical analysis to determine if the participants receiving lorcaserin were able to lose weight, as well as avoiding the risk of cardiovascular events. The median follow-up period was 3.3 years.

What were the basic results?

Safety

During the median follow up of 3.3 years, there was no significant difference in the rate of cardiovascular events between the groups, occurring in 2% per year in the lorcaserin group and 2.1% per year in the placebo group - [hazard ratio HR 0.99, 95% [confidence interval CI 0.85 to 1.14).

There was no difference between the groups for any individual cardiovascular event.

Adverse events of special interest were uncommon, and the rates were generally similar in the group receiving the drug and the group receiving placebo, except for a higher number of people with serious hypoglycaemia (low blood sugar) in the lorcaserin group (13 vs 4).

Weight-loss outcomes

The average weight loss over 40 months for participants receiving lorcaserin was 4.2kg compared to 1.4kg in the placebo group, resulting in a 2.8kg difference.

After following up for 1 year, weight loss of at least 5% had occurred in 1,986 out of 5,135 patients (38.7%) who received the lorcaserin drug, and 883 out of 5,083 (17.4%) in the placebo group (odds ratio (OR) 3.01, 95% CI 2.74 to 3.30).

After 1 year, weight loss of at least 10% was more likely in the lorcaserin group, occurring in 748/5,135 (14.6%) compared with 243/5,083 (4.8%) of the placebo group (OR 3.4, 95% CI 2.92 to 3.95).

Average BMI remained in the obese category for both groups, differing by only 1 point after 1 year. For the lorcaserin group BMI decreased from 34.9 to 33.4 compared with from 35 to 34.3.

How did the researchers interpret the results?

The researchers state that in a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.

Conclusion

This randomised controlled trial has shown that for obese people with cardiovascular disease or cardiovascular risk factors, lorcaserin appears to be safe and does not increase the risk of heart attack, stroke or death from either. However, it does not appear to lead to substantial weight loss either.

For people who have exhausted all options when trying to lose weight, the results of this study suggest lorcaserin could provide a slight reduction in weight. However, this drug is only approved in the US, and currently does not have a licence in Europe. In the UK, it would need to be approved by the National Institute for Care Excellence (NICE) before it could be prescribed for weight loss.

There are a number of limitations to note.

It is not possible to tell whether lorcaserin will help people maintain weight loss, as this study could only show a small amount of weight loss over a period of 40 months. Studies with a longer follow-up period are needed to determine long term outcomes.

The average age of the participants in this study was 64, meaning it's not possible to tell whether this drug is suitable as a weight-loss strategy for younger people.

It is unclear whether people engaged with the diet and exercise programmes or utilised the dietitian. As there were 473 sites in 8 different countries it is likely that there were differences in the advice and exercise programmes in each centre.

It is also important to remember that lifestyle changes such as altering diet and exercise should be the priority when trying to lose weight, rather than relying on a drug for treatment. For anyone trying to lose weight, there is support available from the NHS. More information on losing weight can be found here.