Obesity Part 1 – drug treatment

This week’s illustration is the Willendorf Venus, circa 25,000 BC, the oldest known man-made representation of the human form. There is nothing new about obesity!

Medication for Obesity

The next few blogs will look at the increasing problem of obesity. I am taking this out of order – starting with the use of drugs to control weight because this is receiving so much media attention just now.

The world of discarded and discredited medication is littered with anti-obesity drugs. Thyroid hormone, amphetamine, orlistat, fenfluramine and phentermine for a start – and a good few more. None were particularly effective and most were withdrawn from the market because they had unacceptable side effects. The received wisdom has been, until now, that pills are pretty useless for aiding weight loss.

A new era?

Maybe – with the finding that certain anti-diabetic drugs are very effective in promoting weight loss. The main ones belong to a group known as GLP-1 agonists and include semaglutide and liraglutide. They are self-administered by weekly or daily injections and have been found to reduce weight loss of about 15% of body weight over a year.

The discovery of this property of  GPL-1 agonists has led to tremendous excitement among doctors and drug companies and a veritable deluge of publications – of which I will try to make some sense. This form of treatment has led not only to excitement but also to much concern about how this medication should be used and what might be the downsides.

The naming of parts (apologies to Henry Reed):

A short introduction to the arcane world of drug nomenclature. (you might also find this a useful lesson for understanding your medication). All drugs prescribed by the NHS have at least two names – the pharmacological name (ie paracetamol with a small p) and the trade name (ie Panadol with a large P). Some drugs can have several trade names when they are produced by more than one pharmaceutical company, after their protected period has expired. Occasionally a drug produced by a single drug company has two names, if they are for different indications and perhaps produced in different formulations. The GPL-1 antagonists fall into this two-name category – the formulations for treating diabetes and the formulations for weight loss.

GLP-1 antagonists

These seem to work by reducing the appetite, perhaps by slowing stomach emptying. At the moment there are two candidates:

• semaglutide whose trade names are Ozempic for treating diabetes and Wegovy for weight loss. Wegovy is given by weekly injections (there is also an oral version in development) and as mentioned above gives an average weight loss of about 15% of body weight over a year. This is the most popular drug for weight loss and has been approved for this use both in the USA and the UK. Our regulatory body, The National Institute for Health and Care Excellence (NICE), has decreed that it can be prescribed for those with a BMI of 37 kg/m2 and at least one weight-related complication such as diabetes or high blood pressure.
• liraglutide whose trade names are Victoza for treating diabetes and Saxenda for weight loss. Liraglutide is given by daily injection and is less effective than semaglutide.
• AN Other. The value of shares in the makers of Wegovy, Novo Nordisk Pharmaceuticals, has risen by 165% over the past two years and it is no surprise that other drug firms are producing their own versions. There are several serious competitors in the wings such as  retatrutide which can reduce weight by 24% in a year and tirzepatide (Mounjaro) which is as effective. Tirzepatide is approved in the US for treating diabetes and is awaiting approval for obesity. More, similar, “me too” drugs are only just around the corner.

The answer to a maiden’s prayer?

It does sound like it doesn’t it? Just give yourself a jab once week  and forget about all the suffering of going on a diet and sweating it out at the gym. But there may be snags.

• What happens when you stop the medication? As you might expect, the weight piles on again. NICE recommends that Wegovy be used for not more than 2 years initially. However others have suggested that once started it should be continued indefinitely. The costs and side effects might be predicted to multiply.
• What about the side effects? The main ones affect the gut with symptoms such as nausea, vomiting, abdominal pain and diarrhoea. Wegovy has also been linked to depression, suicide and suicidal ideation.
• What about costs? These are large and vary widely depending on the source. Cost for one month of Wegovy varies from about £200 to over £1,000.
• Who will pay for it? At the moment most prescriptions are filled privately – it is not difficult to organise these on the internet. The most recent proposal is for a “controlled and limited launch”. Wegovy will be prescribed via specialist NHS weight management services alongside diet and exercise recommendations.
  The potential cost to the nation could be enormous. Analysts estimate that the global market could be worth £$100 billion. It might be argued that there are savings through the prevention of heart disease and other ill effects of obesity. However it is a truism that there is no drug treatment which reduces health service costs over time – if you avoid illness and death from one cause you will cost the NHS more in the long-term because of all the other conditions you will go on to contract. Exercise is the only treatment which reduces long-term illness costs because it also reduces the risk of all the other non-communicable diseases.
• Are there other benefits? Yes, Wegovy does reduce the risk of heart disease and heart failure and strokes by up to one fifth. Cardiologists may now need to add this group of drugs to the already long list of drugs which they prescribe to their patients.
• Will these drugs be used for their cosmetic effects? Almost certainly there will be people of a normal or only slightly increased weight who will clamour for this treatment to get more beach-body ready.
• What about supplies? Indeed. Already semaglutide is in short supply. A recent BMJ highlit the fact that clinicians in England are being advised that they cannot prescribe appetite suppressants for patients with type 2 diabetes until at least the middle of next year, because of ongoing shortages. Some doctors and medical experts have warned that people in Britain who can afford to pay out of their own pocket may get easier access to Wegovy than those seeking treatment in the NHS.

A final thought

I am very worried by the prospect of yet more use of drugs to replace lifestyle choices. Wegovy and its relatives are no substitute for exercise and a healthy diet.

Remember to keep active and  Caveat Emptor!