Could a new appetite-controlling drug be the answer to obesity?

We need effective strategies for the prevention and treatment of obesity as much as for COVID-19. According to NHS data published in May 2020, 26 percent of men and 29 percent of women in the UK were estimated to be obese - defined as having body mass index greater than 30.

The situation may now have deteriorated owing to lockdown-related weight gain. Not only are obese patients more likely to die from COVID-19, but recent estimates by researchers at the University of Glasgow suggest that obesity may have overtaken smoking as a cause of ill-health in England and Scotland.

A healthy balanced diet combined with appropriate levels of physical activity can prevent weight gain, but it is not an effective treatment for obesity. Very low-calorie diets, consuming less than 1,000 kcal per day, can result in weight loss of 10-15kg in up to 12 weeks.

And more modest moderate calorie restriction, as used by most commercial slimming plans, can result in an average weight loss of around 7kg a year. However, any weight lost by these methods is usually regained, so another approach is needed.

To date, most drugs developed to treat obesity are either ineffective in clinical practice or have nasty side effects such as increasing blood pressure or causing anal leakage. Bariatric surgery is currently the only effective treatment for severe obesity but it comes with risks and long-term side-effects.

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A series of peptide hormones are secreted in the intestine that sense food energy intake and play a role in regulating appetite and energy expenditure. One reason why bariatric surgery is so effective is because it changes how the gut responds to food intake and talks to the brain.

In particular, glucagon-like peptide (GLP-1) is secreted in the ileum, the final section of the small intestine, in response to carbohydrate-containing foods. This promotes insulin synthesis and secretion in the pancreas, but it also has an effect on the stomach, reducing the movements of the digestive system and acid secretion.

A ground-breaking large double-blind trial in otherwise healthy, obese patients without diabetes was published in February in the New England Journal of Medicine by UK researchers led by John Wilding involving semaglutide: a drug that mimics GLP-1 that was originally developed to treat diabetes but found to cause substantial weight loss in patients with type 2 diabetes.

The researchers recruited 1,961 patients, 75 per cent of whom were female, 75 per cent white, 13 per cent Asian, and 6 per cent black, with an average body mass index of 38 and randomly allocated them into two equal groups. One group was given weekly injections of semaglutide and the other, the control group, was given placebo injections for 68 weeks. Both groups also received diet and life-style advice.

The patients in the semaglutide group lost an average of 15.3kg compared with 2.6kg in the control group. The treatment effect, the difference between the groups, was a 12.7kg weight loss.

The treatment also lowered blood pressure by 5.1mmHg and patients reported improved physical functioning. The main side effects of treatment were nausea, sometimes vomiting and diarrhoea, though gastrointestinal disorders were also more frequent in those on the active treatment. Of concern may be an increased risk of gallbladder disease and pancreatitis.

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While this high-quality trial shows semaglutide promotes a greater weight loss than any other drug so far tested, what happens when treatment stops is uncertain. Preventing weight regain is a major challenge and the lesson from bariatric surgery is that patients need to avoid unhealthy snacking and sugar sweetened beverages in addition to downsizing portions of high calorie foods.

Confirmation of these research findings is also needed in a more ethnically diverse population with a higher proportion of men. And from a practical standpoint, the requirement for weekly injections of the drug is likely to limit a wider roll out of this treatment. However, oral preparations of this class of drug have been developed and are undergoing trials.

While semaglutide looks like a promising treatment for severe obesity, it is not a magic bullet. We must continue to promote a healthy lifestyle as well measures to discourage the adoption of the unhealthy eating habits that are causing obesity. It is rather like the situation we are in with the COVID-19 and the vaccines - we still need to stick with public health measures and not become overdependent on medicines.