An update from the Society's Metabolic and Obesity Endocrine Network

So it’s official: obesity is now recognised as a complex chronic disease with significant morbidity and mortality. One of its main metabolic complications is type 2 diabetes, and the two conditions share key pathophysiological mechanisms. The diagnosis of obesity is, however, complex, and one size does not fit all.

A CHANGE OF LIFESTYLE?

Lifestyle interventions can be impressive, as evidenced in the DiRECT trial. After two years of follow-up in the intervention arm, where participants received a very low calorie diet (an 825–853kcal/day formula diet for three to five months), followed by food reintroduction and structured support for weight loss maintenance, 11% of participants lost ≥15kg and overall diabetes remission at two years was 36.5%.

Typically, most lifestyle interventions result in progressive weight loss over six months, followed by plateau and weight regain over a period of one to three years. The need for obesity management services to enable long term support of these individuals with lifestyle counselling and access to relevant multidisciplinary teams is clear.

THE ROLE OF SURGERY

Surgical weight loss beats diet and exercise for reversing diabetes. The impact of gastric bypass surgery in most randomised controlled trials typically results in a 20–25% decrease in body weight, which is sustained with improvements in metabolic control. More importantly, the extensive experience with bariatric/metabolic weight loss shows that this sustained reduction in weight leads to reduced mortality and morbidity, for example from cardiovascular disease, and surgery is highly cost-effective.

Although it appeared that the surgeons were sharpening their knives and taking centre stage in the management of the condition, it wasn’t quite time for the endocrinologists to exit. Post-bariatric hypoglycaemia was recognised to be a major side effect. Symptomatic hypoglycaemia may be experienced by one person in three, but severe hypoglycaemia (which can be life-threatening with altered consciousness) may be experienced by one in a hundred.

This side effect is a serious problem, affecting patients’ ability to work or drive, and causing psychological damage. No guidelines exist, and the evidence base for management is relatively small. Advice with respect to driving licensure and the use of glucose monitors across the country is inconsistent.

The Society’s Metabolic and Obesity Endocrine Network has been working hard to solve this, by drawing up a set of consensus guidelines.

MEDICAL INTERVENTION

We now live in interesting times for the medical treatment of obesity. Recent data from trials of the high dose glucagon-like peptide-1 (GLP-1) analogue semaglutide and the novel glucose-dependent insulinotrophic polypeptide/GLP-1 receptor agonist tirzepatide suggest that people with obesity can lose between 15–20% body weight. Is it now time for a rethink?

Although these are impressive headline figures, the limited length of the trials for these agents and the cumulative high cost will mean that they can only be employed for relatively short periods of time (e.g. two years for high dose semaglutide), and in limited populations defined by high body mass index and the presence of co-morbidities. Moreover, it is presently unclear whether these new treatments will have a significant impact on the co-morbidities of obesity and overall mortality. Early data on liver fat clearance with tirzepatide are promising and being fully evaluated in the SYNERGY trial.

WHAT NEXT?

So is it now time to put away the knives? We argue that both surgery and the newer drugs will have their place in the management of obesity.

However, a serious effort to prevent the development of obesity in childhood is required, to head off the tsunami of obesity which we face, and the clear socioeconomic inequalities of this disease. The ‘obesogenic’ food environment does not support those on lower incomes to choose healthy diets. The prevalence of obesity in children from deprived areas in the UK is 20% among those at reception age, approximately double that seen in children from more affluent areas. Affordability, availability and the marketing of less healthy food and drink products all contribute.

The Soft Drinks Industry Levy has shown that legislation can make a small difference in population sugar consumption, but larger governmental efforts are required to ‘move the needle’ sufficiently to alter the upwards trajectory of obesity. Which is why the proposed removal of the obesity strategy by the incumbent government is disappointing.

Shareen Forbes
University of Edinburgh

Tricia Tan
Imperial College London

Gavin Bewick
King’s College London

Shareen Forbes and Gavin Bewick are the Clinical and Science Convenors for the Society’s Metabolic and Obesity Endocrine Network. Post-bariatric hypoglycaemia guidelines are currently being drawn up by the multidisciplinary Metabolic and Obesity Endocrine Network working group.

Learn more about our Endocrine Networks