How to ‘drug’ our way out of the obesity crisis (or not): the roll-out of semaglutide

Nada Khan is an Exeter-based GP and clinical academic, and an Associate Editor at the BJGP.

Obesity is a complex condition, affecting one in four adults in the UK.  The challenge of managing obesity and its related comorbidities impacts on patients, practice and services.  Given its growing prevalence and associated diseases, if there was a magic cure for obesity we’d all be recommending it.

Semaglutide (marketed as WeGovy) promotes weight loss by mimicking the action of glucagon-like peptide (GLP-1), which slows down gastric emptying, increases a feeling of fullness and promotes insulin release.¹ The marketing and press hype around semaglutide has made it seem like a magic wonder drug, and it’s increasingly common to see patients coming into practice asking for it.  A recent update from the National Institute for Care and Excellence (NICE) has recommended its use for weight loss with a few important provisos.² With increasing numbers of patients unclear on how to access semaglutide, what do GPs need to know?

The trial evidence

The Semaglutide Treatment Effect in People with Obesity (STEP) program’s STEP 1 study was an international randomised double-blind trial comparing semaglutide injections alongside lifestyle interventions against a placebo in patients with a BMI of 30kg/m², or people with a BMI of 27-29 kg/m² with weight-related comorbidities such as hypertension or sleep apnoea, though people with type 2 diabetes were excluded from the trial.³  The lifestyle interventions were not insignificant.  Participants in the intervention arm monitored their daily calorie intake and exercise, and these logs were reviewed during monthly individual counselling sessions to help maintain a low-calorie diet and increased physical activity.³

Criteria for accessing semaglutide

NICE has provided specific recommendations for offering semaglutide based on how the STEP 1 intervention was delivered, and these criteria currently preclude its use in general practice.  Semaglutide is only recommended for use within a multidisciplinary specialist weight management service offering concurrent lifestyle advice on diet and exercise to mirror the lifestyle interventions offered in the STEP 1 trial.  People accessing it must have a BMI of at least 35 kg/m², or a lower BMI threshold of 30 kg/m² with a complex comorbidity or are from certain higher-risk ethnic groups.²  The NICE guidance does suggest that semaglutide can be offered outside of Tier 3 and Tier 4 weight management services, and you don’t have to look too far to find private GPs happy to prescribe semaglutide ‘in accordance with NICE guidance’.  But because most GPs cannot offer in-depth lifestyle advice, adjustments to scale up to the maintenance dose or monitor for side effects without extra funding or capacity, it’s not currently a viable option in NHS general practice.

Access to semaglutide within the NHS is dependent on specialist weight management services which are not equally distributed throughout England and creates, as the NICE committee suggests, a ‘post code lottery’.²  The government has announced a two-year pilot to look at widening access to GLP-1 agonists outside of specialist weight management services, including looking at how GPs could safely prescribe these medicines.  These pilots are still in development and for GPs and local commissioning teams there will need to be clarity on specific support to provide semaglutide in the same way it was offered within the STEP 1 trial.  This planned GP pilot programme will in theory aim to reduce inequities and patchy access, but it is very uncertain how general practice will be able to deliver the capacity for the behavioural weight management support needed for delivery alongside semaglutide.

Longer-term use of semaglutide

The current NICE guidance states that semaglutide should be used for a maximum of two years, despite patient experts on the NICE committee describing the challenge of maintaining long-term weight loss. So why the two year limit?  The longest treatment duration for semaglutide in a clinical trial was studied in the STEP 5 trial, which followed a similar approach to STEP 1 but provided the intervention to significant benefit over a two-year period.⁴  NICE was unable to make any firm conclusions on use beyond this time frame because there is no evidence from longer-term trial data for maintenance use of semaglutide, though Novo Nordisk (which manufactures the drug) pessimistically assumed that three years after stopping semaglutide the weight loss advantage would be lost compared with those who never took semaglutide.  The committee’s decision was also influenced by NHS provision for specialist obesity services under Tier 3 services, which are currently delivered over a two year time frame, and longer-term use was also deemed to be less cost effective.

Weight regain is common after withdrawal of weight loss interventions and semaglutide is no exception.  An extension analysis of the STEP 1 trial including 327 participants showed that participants taking semaglutide regained an average of two-thirds of their weight loss after a year off-treatment of not taking semaglutide or having the same in-depth lifestyle interventions.⁵  These results, the authors of the extension study suggest, mean that pharmacological treatments like semaglutide should be maintained in the long-term to confer sustained benefit for people with obesity.  But unfortunately, that’s not how it’s currently been recommended for use by NICE.

What can we do?

With the weight loss effects of semaglutide and other GLP-1 agonists so widely reported in the press and social media, it’s not just people with obesity and weight-related comorbidities that are asking about it.  But ask they will, so what we can do is be armed with information about it.  We need to be able to explain the referral criteria, including BMI thresholds.  We also need to explain that semaglutide is not a stand-alone treatment, and is only recommended for use as a package of care offered by a specialist weight management service.  And to counter the perception of semaglutide as a magic cure, we can explain that the evidence for long-term weight loss after stopping semaglutide is uncertain, and that most people will regain some of the weight that they lose following treatment.  The British Heart Foundation has a website explaining the referral criteria and use of semaglutide that can be added to practice websites or sent to patients wanting further information.

Going back to that idea of a magic cure, how is the use of GLP-1 agonists going to solve the global obesity epidemic?  Some commentators have said that we can’t ‘drug our way’ out of an obesity crisis that has its roots in wider societal issues.  The National Food Strategy, led by Henry Dimbleby, aimed to tackle the ‘broken’ food system that has led to increased rates of obesity and included 14 recommendations to improve the national diet, tax junk food, reduce diet-related inequalities and change how we grow our food. And did the government listen?  Well, no. Dimbleby resigned from his role as the government’s ‘food tsar’ in 2023 as a form of protest against the government’s strategy towards obesity, frustrated by ongoing inaction and a failure to take forward most of the National Food Strategy recommendations, whilst instead focussing on anti-obesity drugs such as semaglutide.⁶  Here in the BJGP, Elizabeth Dapre described introducing temporary weight-loss interventions like semaglutide without thinking about meaningful top-down approaches to tackle the underlying issues contributing to obesity akin to ‘sprinkling teaspoons of water onto an increasing blaze’, a strategy that will never work.⁷

So a magic cure it is not, but semaglutide may well be of benefit in the short-term to some people.  Longer-term efficacy data would be helpful to guide recommended length of treatment and to limit the known weight re-gain associated with stopping treatment.  Complex systems need complex solutions, and for some, the real magic solution the obesity crisis needs will be rooted in stronger interventional policy to fix the food system and our relationship with unhealthy eating.

References

1. Chao AM, Tronieri JS, Amaro A, Wadden TA. Semaglutide for the treatment of obesity. Trends Cardiovasc Med. 2023;33(3):159-66.
2. Semaglutide for managing overweight and obesity. National Institute for Health and Care Excellence; 2023 8 March 2023.Contract No.: T1875.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
4. Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-91.
5. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-64.
6. Smyth C. UK can’t drug its way out of obesity problem, says ex-food tsar. The Times. 2023 20 April 2023.
7. Dapre E. Are GLP-1 agonists the answer to our obesity epidemic? Br J Gen Pract. 2023;73(733):365.