Terry Maguire evaluates the road ahead for Wegovy, a weight-loss drug that we will all be familiar with soon enough
The Fat Islands
With 66 per cent of population of the UK and Ireland overweight or obese and the National Health Services all too aware but largely ignoring this fact, we are facing into a significant public health crisis that is already with us. Wegovy (semaglutide) is a medicine everyone knows, or will know soon enough, and is being promoted as the panacea for our corpulence and a game- changer in the war against obesity. Wegovy is the most famous medicine we don’t have. Yet in its absence, the medicine is already licensed in the UK, so it’s accepted as safe and effective.
The National Institute for Health and Care Excellence (NICE), the body that decides if a medicine is to be available on the Health Service, has decided it can be prescribed for patients in Tier 3 and Tier 4 weight management services, mostly specialist centres in hospitals and which covers about 35,000 patients — not very many, given the 12 million who potentially need treatment. NICE guidance generally applies to N Ireland, but we don’t have Tier 3/4 weight management services, so a “managed entry” process will apply when it arrives at the end of 2023. In June, the UK government announced a pilot to add 40,000 patients to treatment by GPs and to determine the medicine’s real-world effect. Prime Minister Rishi Sunak is keen to see how the drug might perform but the pilot only applies to England as Health Services are devolved.
DO NOT PRESCRIBE
Indeed, in N Ireland, SPPG — the Health Board — has written to healthcare professionals stating that the drug would not be available on prescription at this time and it was asking private medicine providers to comply with this Health Service restriction. This is a really interesting request, given that private supply of another GLP-1 — Saxenda — is already rife in nail-bars, hair salons and pharmacies and is likely to increase massively once UK supplies of Wegovy arrive.
In May, medicines inspectors raided a number of retail premises and confiscated scores of ‘skinny-jab pens’. Some are claiming ignorance of the Medicines Act 1968 but this will not be a good defence. Pharmacies, both online and in bricks and mortar, are the main source of the private legal supply of Saxenda and are keenly awaiting Wegovy as a once-weekly injection, which is always more acceptable to a daily injection, and this drug is possibly more effective.
THE NEW WONDER DRUG
Wegovy is certainly effective. It gives the user a constant feeling of satiety, therefore calorie intake is massively reduced and weight is lost. The STEP (Semaglutide Treatment Effect in People with Obesity) trails, a series of Phase 3 clinical trials in different settings, have produced impressive results. The STEP-1 trail, published in New England Journal of Medicine, measured the effectiveness of Wegovy over 68 weeks. Wegovy patients lost 14.9 per cent of body weight compared to 2.4 per cent loss in the placebo group. Both groups had intense advice on nutrition and exercise and were given behavioural support.
This result is significant, as it makes Wegovy about twice as effective as other weight-loss medicines such as sibutramine and rimonabant, where studies recorded 5-to-9 per cent of body weight loss. Lifestyle advice plus behavioural support got a 3-to-5 per cent loss. Studies suggest the Wegovy is largely safe and it is currently licensed for two years’ use, but there are studies soon to be published that might extend this to five years.
MEDICINE OR BEHAVIOUR CHANGE?
Whereas debate may continue on whether obesity is a disease, a syndrome or a natural response to an abnormal environment, there remains little disagreement on the causal link between obesity and illness. Logically therefore,
as with other conditions such as raised blood pressure, effective drug intervention should be effective and provided.
Yet for obesity, to date, the question of whether a drugs or a lifestyle intervention is superior has been in favour of lifestyle intervention; better diet and increased activity have been proved effective in reducing morbidity and morality, but too many people struggle to achieve meaningful targets.
Whereas the risks associated with obesity increase alongside weight-gain in a linear fashion, the risk reduction with weight loss, with or without medication, is much more dramatic in scale than the actual degree of weight lost. A loss of 10 per cent of body weight equates to a loss of 3 per cent of visceral fat, which is accompanied by a dramatic improvement in overall health risk. Yet it must be remembered, particularly with regard to older drugs, now no longer used, that even where a drug is capable of affecting a 5 or 10 per cent weight loss, this does not necessarily mean an individual’s disease risk drops by the same percentage. A side-effect of the drug might increase a patient’s cardiovascular risk to offset the health benefit and therefore use of the drug cannot be justified. For this reason, many drugs effective in reducing weight are no longer licensed for the management of obesity.
Losing weight is difficult. Individuals with insulin resistance, for instance, have been shown to lose weight only half as successfully as others by whichever means is attempted. NICE advises that drug therapy should be considered for patients who have not reached their target weight loss, or have reached a plateau with dietary, activity and behavioural change alone. Only two drugs are licenced and currently available for weight-loss: Orlistat and liraglutide (Saxenda). Most drugs failed as risks outweighed benefits.
Sibutramine (Reductil) and Rimonabant (Acomplia) lost their marketing authorisation soon after launch because of side-effects.
A ROCKY ROAD
Some of the most toxic substances known have historically been used to induce weight loss, including mercury, arsenic, strychnine and dinitrophenol. Perhaps the most notorious of the anti-obesity medicines were the amphetamines (ie, Dexamyl, Eskatrol, Dexedrine, Didrex) some of which, to compound the felony, were combined with barbiturates (Ambar) in order to minimise side-effects. The noradrenergic appetite suppressants, phentermine and diethylpropion, are still used for weight-loss in the US, although their use is limited because of adverse effects and they can only be used in the short- term (a few weeks). Phentermine and diethylpropion are not prescribable on the NHS because the evidence-base for their use in long-term obesity management is non-existent, in spite
of being used for over 40 years. They are, however, still prescribed privately, usually at great expense, through a regulatory loophole. Phentermine is commonly used in the US and elsewhere for rapid short-term loss, but rapid and rebound weight gain associated with its use remains problematic.
So far, for Wegovy, everything looks promising but there is a stoney road ahead and I suspect with its cost to
the taxpayer, the rebound in weight on cessation and possible emergence of side-effects not yet identified, we are some way off Wegovy’s panacea claim.
Terry Maguire owns two pharmacies in Belfast. He is an honorary senior lecturer at the School of Pharmacy, Queen’s University Belfast. His research interests include the contribution of community pharmacy to improving public health.