Clinical briefing: the rise of weight loss drugs

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Wegovy (semaglutide) is one of the few drugs, alongside Viagra, aspirin and penicillin, that the public widely recognises. While its popularity has been boosted by celebrity endorsements, there is a real clinical need: in 2022, 28.9 per cent of adults in England were obese.¹ 

The popularity of weight loss drugs is not surprising. An article in the BMJ describes them as “more effective than widely available community (non-specialist) weight management services but less effective and invasive than bariatric surgery, which is restricted to adults with severe obesity”.² 

In December 2024, NICE approved the use of tirzepatide, an agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptors, for weight loss and weight management in adults aged 18 years and over. 

According to Dr Kath McCullough, NHS England’s national specialty adviser for obesity: “Obesity is one of the greatest public health issues facing the NHS and weight loss drugs, such as tirzepatide, are an important tool in helping people lose weight while also reducing the risk of other serious long-term conditions such as diabetes, strokes and heart attacks. However, on their own, weight loss drugs are not a magic bullet.”

Proof of efficacy

Tirzepatide, added to lifestyle counselling, is undoubtedly effective. A trial involving 2,539 participants found that after 176 weeks, placebo users lost a mean of 1.3 per cent of their bodyweight, compared with 12.3, 18.7 and 19.7 per cent for those using subcutaneous tirzepatide 5mg, 10mg and 15mg once weekly respectively.

At the start of the trial, 1,032 participants had prediabetes. At the end of the 176 weeks, 13.3 per cent of placebo users had developed type 2 diabetes, compared with just 1.3 per cent of tirzepatide users.³ 

Not everyone benefits from weight loss drugs to the same extent: 87 per cent of people treated with tirzepatide 15mg once weekly lost at least 5 per cent of their bodyweight, which means that more than one in 10 did not achieve this relatively modest loss. 

However, 35 per cent of those who received tirzepatide 15mg once weekly lost at least 25 per cent of their bodyweight. A 25 per cent loss would move a slightly obese person (32kg/m²) into the healthy range (24kg/m2). 

Clinical studies enrol relatively selected populations, but a real-world study also demonstrated tirzepatide to be effective. It found that people using the treatment as part of the Juniper app-based weight loss service lost an average of 13.8 per cent after 16 weeks. 

Between 96.3 and 97.0 per cent of participants lost at least 5 per cent of their bodyweight, while between 36.9 and 43.0 per cent lost at least 15 per cent.⁴

Health inequalities 

Generally, only people with BMIs of at least 35kg/m2 are eligible for NHS weight loss drugs.2 NICE recommends tirzepatide alongside a reduced-calorie diet and increased physical activity in adults with initial BMIs of at least 35kg/m² (2.5kg/m² lower for several ethnic backgrounds) and at least one weight-related comorbidity. Yet overweight people and those with class I obesity (BMI 30-34.9kg/m²) account for much of the population health risk associated with excess weight.²

Obesity is also strongly linked to socio-economic status – and many of the people in greatest need cannot afford private weight loss drugs, leading some to believe that these medicines are likely to widen health inequalities. 

In 2022, 21.4 per cent of men and 22.7 per cent of women in the least deprived quintile in England were obese compared with 31.5 and 40 per cent respectively in the most deprived areas.¹ 

Huge demand

The NHS is nowhere near treating all those who could benefit from weight loss drugs. The Obesity Health Alliance notes that 4.1 million people in England are currently eligible for semaglutide for weight loss. NHS projections estimate that by 2028, fewer than 50,000 people a year will receive semaglutide for this reason, despite new funding. 

Some 3.4 million people in England are eligible for tirzepatide, which costs between £92 and £122 for a four-week supply, depending on the dose. NHSE has requested to roll out tirzepatide over 12 years. 

From March, NHSE will prioritise people with the greatest clinical need, such as those receiving care in specialist weight management services, but will also start offering tirzepatide to patients with the greatest clinical need outside of specialist services this summer. 

NICE estimates that 220,000 people will benefit during tirzepatide’s initial three-year roll-out. It will re-evaluate the situation after this. 

Re-evaluations are, of course, important, as NHS obesity care walks a tightrope between clinical need and cost containment, while juggling health equity and social justice. Whether that balance is kept remains to be seen.

<sub>References
1. fingertips.phe.org.uk/profile/national-child-measurement-programme/data#page/13
2. BMJ 2024; 384:q196
3. New England Journal of Medicine doi: 10.1056/NEJMoa2410819
4. Telemedicine Reports 2024; 5:311-321</sub>