Dr Ahmed Yousseif, Consultant Endocrinologist at The Physicians' Clinic, comments on the weight-loss drug Lorcaserin.
The global obesity crisis in numbers: Obesity is expanding epidemically worldwide. The obesity pandemic is mostly driven by changes in the global food system with plethora of processed, easily affordable, energy-rich, and effectively marketed foods; paralleled by a more sedentary lifestyle and consequential reductions in energy expenditure. The World Health Organisation (WHO) estimates that currently more than 1.9 billion adults (39% of the population) are overweight and 650 million (13% of the population) are obese, with significant and alarming increases noted in the prevalence of childhood and adolescence obesity. In the UK, over 50% of adults are overweight or obese.
Obesity associated co-morbidities: Obesity and overweight are causally associated with a number of co-morbidities (i.e. hypertension, dyslipidaemia, type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnoea, musculoskeletal disorders, colorectal cancer) and increased morbidity. Thus, a diagnosis of obesity results in mounting healthcare costs for the treatment of obesity and obesity-associated diseases. Therefore, currently there is a pressing need for the development of effective preventative and treatment strategies to combat the obesity crisis.
Treatment options for obesity: Available treatment options for overweight and obesity include lifestyle modifications, medical therapies and bariatric surgery. Lifestyle measures such as dieting, increased physical activity and behavioural modification remain the cornerstone. However, these measures result in modest weight-loss with poor weight-loss maintenance. The development of pharmacotherapies for the treatment of obesity has been hampered by adverse side effects. In fact, some previous weight-loss drugs were found to increase the risk of cardiovascular disease, such as heart attacks or stroke, so these drugs were taken off the market.
The weight-loss drug Lorcaserin: Lorcaserin is a drug used to regulate appetite and approved by the USA Food and Drug Administration since 2012 to complement a reduced calorie diet and increased physical activity for long-term weight management. The drug is unlicensed in Europe. Mechanistically, Lorcaserin is a serotonin receptor agonist acting in the brain appetite centres.
A recent major study, the CAMELLIA–TIMI 61 study by Bohula et al., has put Lorcaserin on the spotlight. The study reported promising results for the safety of Lorcaserin and was published in the peer-reviewed, highly prestigious Medical Journal, the New England Journal of Medicine.
The study reported that patients who took the weight-loss drug Lorcaserin lost 2.8kg more than those who took placebo (dummy treatment) over a period of ~40 months. Furthermore, the study researchers found that patients who took Lorcaserin were not placed at increased risk of heart attack or stroke, compared to the patients in the placebo (dummy treatment) group.
What did the CAMELLIA–TIMI 61 research involve?
12,000 overweight or obese patients from 473 different study sites across 8 countries were enrolled to the study. The participants had to have a body mass index (BMI) of at least 27kg/m2, with atherosclerotic cardiovascular disease (blocked heart vessels) or multiple cardiovascular risk factors such as diabetes mellitus and high blood pressure. The median follow-up period was 3.3 years.
The participants were randomised to take either Lorcaserin 10mg twice daily or placebo. All patients were encouraged to participate in a standardised weight-management programme entailing intensive behavioural therapy that included both dietary and exercise information. Participants had unlimited access to telephone dietitian input.
The primary outcome was major cardiovascular events, such as myocardial infarction (heart attack), stroke, unstable angina, heart failure, coronary revascularisation (surgery to unblock heart vessels).
The researchers used statistical methodology to assess whether treatment with Lorcaserin was efficacious in terms of weight loss, while avoiding the risk of cardiovascular events.
What were the key results of the CAMELLIA–TIMI 61 study?
Safety: During the median follow up of 3.3 years, there was no significant difference in the rate of cardiovascular events between the Lorcaserin and placebo-treated groups. Adverse events were uncommon, and the rates of adverse events were comparable in the groups receiving Lorcaserin and the placebo, except for a higher number of episodes of low blood sugar (hypoglycaemia) in the Lorcaserin group.
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. Thus, Lorcaserin treatment resulted in 2.8kg greater weight loss vs placebo.
Is Lorcaserin the "Holy Grail" for weight loss?
In the CAMELLIA–TIMI 61 study the effects of Loracserin on weight loss were only modest, with the Lorcaserin group exhibiting only 2.8kg greater weight loss vs. the pacebo group. Furthermore, Lorcaserin in this study was taken alongside a diet and exercise plan, thus the weight loss outcomes were the combined effect of Lorcaserin, diet and exercise.
Additionally, longer studies are needed to determine whether the weight loss effects of Lorcaserin are sustainable and extend beyond the 3.3 years of the average follow up in the study.
Finally, Lorcaserin comes with a considerable cost of approximately £155 to £225 per month, with annual costs mounting to between £1,860 - £2,700. Lorcaserin is only available to prescribe in the USA and to date has not yet been approved in Europe. So even if Lorcaserin becomes available in the UK market, it is uncertain whether the drug will be funded in the NHS.
Read the full article here: https://www.bbc.co.uk/news/health-45319393