Wegovy: panacea for our obesity epidemic?

With 66% of population of the UK and Ireland overweight or obese and the national Health Services all too aware while largely ignoring this fact, we are facing into a significant public health crisis that is already with us. Wygovey is a medicine everyone knows, or will know soon enough, and is being promoted as the panacea for our corpulence and being identified as a game changer. Wegovy is the most famous medicine we don’t have. Yet in the absence of supply, the medicine is already licensed in the UK so it’s accepted as safe and effective. The National Institute for Health & Care excellent (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 but GPs cannot supply it when it arrives at the end of 2023. In June UK government announce 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 address this crisis 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 GLP-1s – mainly Saxenda- is already rife in nail-bars, hair salons and pharmacies and is likely to increase massively once UK supplies of the 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 on-line and in bricks & mortar, are the main source of the private legal supply of Saxenda and are keenly waiting Wegovy as a once weekly injection is always more acceptable to a daily injection and possibly more effective.

The new wonder drug

Wygovy (semaglutide) 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 semaglutide over 68 weeks and this resulted in a loss of 14.9% of bodyweight in the treatment group compared to 2.4% 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% of bodyweight loss where lifestyle advice plus behavioural support got a 3% to 5% loss. Studies suggest the drug is largely safe and it is currently licensed for 2 years use but there are a number of studies soon to be published that might extend this to 5 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 morbidity and mortality. Logically therefore, as with other conditions such as raised blood pressure, effective pharmacological intervention should be effective and provided.

Yet for obesity, to date, the question 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% of body weight equates to a loss of 3% of visceral fat, which is accompanied by a drastic 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% 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 liguratide. 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 (e.g. 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.

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