Olivia Hillary was over the moon when she was prescribed Mounjaro on the NHS to control her type 2 diabetes.
While GLP-1 drugs such as Mounjaro are better known for weight loss, they were actually developed for type 2 diabetes and Olivia was desperate to improve her health.
She had tried ‘every diet going’ since she began gaining weight at the age of 17. ‘I’ve joined slimming clubs and tried meal-replacement diets, but nothing worked long term,’ says the 39-year-old mental health nurse.
Her weight had affected her health, too. By 2023, Olivia weighed 18st (at 5ft 7in she had a BMI of more than 40; over 27.5 is classed as obese), and as well as high blood pressure, she was living with uncontrolled type 2 diabetes.
‘I felt like I’d hit a wall,’ says Olivia, who lives in York with partner Myles, 39, an HGV driver.
‘My medications for diabetes weren’t working, my mood was always up and down and my weight remained high. I didn’t know what else to do – and the offer of Mounjaro felt like a way out and gave me hope there was a brighter future around the corner.’
At the time, her HbA1c level – a measure of the average ‘sugariness’ of the blood over three months – was 78mmol/mol, well above the cut off for type 2 diabetes, which is 48.
Olivia was also hopeful Mounjaro would help reduce her food cravings and aid weight loss.
GLP-1 agonist drugs such as Mounjaro and Ozempic work by mimicking glucagon-like peptide-1, a hormone in the body that slows digestion and signals fullness to the brain, silencing ‘food noise’. As a result, most people feel satisfied quicker and eat less.
‘As someone who was constantly thinking about food – it felt as if the fridge was always calling – it sounded like something that might finally switch off that “food noise”,’ says Olivia.
By 2023, Olivia weighed 18st (at 5ft 7in she had a BMI of more than 40; over 27.5 is classed as obese), and as well as high blood pressure, she was living with uncontrolled type 2 diabetes
And she’d seen first-hand what these drugs could do. Myles, who also had type 2 diabetes and a BMI of nearly 40, had lost 5st after being prescribed Ozempic on the NHS and his diabetes had been brought under control.
Olivia began on weekly 2.5mg Mounjaro injections – over six months, the dose was gradually increased to 10mg – and she was determined to make it work. ‘I followed the instructions on how to inject myself to the letter; cut down on portion sizes; practised mindful eating – eating slowly and removing distractions; and I walked my dog for an hour a day,’ she recalls.
Initially she lost a few pounds but, she says, ‘that was more due to my willpower than a lack of appetite. The drug clearly wasn’t working as I still felt so hungry all the time.’
At mealtimes, she and Myles ate the same food, ‘but he’d feel full and stop before finishing his plate. I could easily have eaten mine and finished his, too. I started to wonder what was wrong with me.’
Despite this, Olivia has persisted with her weekly injections, hoping the effects would kick in.
Yet two-and-a-half years later, her diabetes is still not under control – and she still weighs 18st, with a BMI of 40.2. She remains on the drug as it seems to have controlled her chronic thrush infection. ‘I am so disappointed I haven’t lost weight’ she says. ‘I posted about it on social media, and from the response I got it’s clear I’m not the only one.’
Olivia is now on the waiting list for bariatric (weight-loss) surgery. While the vast majority of people taking GLP-1 drugs lose significant amounts of weight, a sizeable minority do not, something many of those on them may not realise.
A 2025 study involving around 480 people attending an obesity clinic found that almost one in five – nearly 20 per cent – were classed as ‘non-responders’, meaning they lost less than 5 per cent of their body weight, reported the BMJ Open.
The figure is higher than in drug trials, where around 5 per cent were found to be non-responders.
‘Some people have a low sensitivity to GLP-1s, and just hammering that system with higher doses will not produce sufficient results,’ says Dr Simon Cork, a senior lecturer in physiology at Anglia Ruskin University.
Professor Giles Yeo, a molecular endocrinologist at the University of Cambridge, says that while trials show around 20 per cent of people don’t lose weight on GLP-1s, there will be practical reasons for this, such as stopping taking the drug due to side-effects or they can’t afford it.
He puts the number who genuinely can’t lose weight on the drugs at around 5 per cent. This may be largely down to genes.
A study just published by the University of Copenhagen identified two gene variants linked to how much weight people lose on the weight-loss injections.
Dr Cork adds that the underlying reason an individual develops obesity can also vary – this may in turn affect how they respond to the drugs. For instance, a GLP-1 drug wouldn’t help with weight gain due to an underactive thyroid, as it is caused by a hormone imbalance.
It’s the same with polyendocrine metabolic ovarian syndrome (PMOS, previously called polycystic ovary syndrome) – which Olivia has – a common hormonal condition that affects how the ovaries work and the way the body processes energy and stores fat.
Dr Cork adds that hundreds of genes can predispose someone to weight gain, each contributing a small but cumulative effect.
A lack of response to medication is a widespread issue across many commonly prescribed drugs.
‘The effects of drugs are far more uncertain than we expected ’ Professor Barber tells Good Health
For instance, research suggests antidepressants, strong painkillers (e.g. codeine and tramadol) as well as blood thinners (e.g. warfarin and clopidogrel) do not work effectively for everyone.
Indeed, as a 2015 study, published in Nature, found, the ten bestselling drugs in the US only worked in a quarter of patients – and half didn’t work in 90 per cent of patients.
These included the heartburn drug omeprazole, which helped only one in 25, and the statin rosuvastatin, which helped one in 20, as Nick Barber, a professor emeritus of pharmacy at University College London, points out in his new book, How To Take Drugs.
‘The effects of drugs are far more uncertain than we expected – and because of that we need an approach to decide whether to take them, stay with them or stop them,’ Professor Barber tells Good Health.
And, increasingly, scientists are looking at the role of genetics in drug metabolism, known as pharmocogenetics, with some experts arguing genetic testing should be offered more widely to help doctors and pharmacists tailor treatment according to how an individual will respond to medications.
‘Your genes can affect how your liver breaks down a medicine, for instance, and how your body responds to it,’ explains Professor Amira Guirguis, chief scientist at the Royal Pharmaceutical Society. ‘They can also determine whether a drug binds properly to its target in order to produce a response in the body.’
Indeed, as many of 89 per cent of patients aged 70 and above had been prescribed at least one drug affected by their genes over the previous two decades, according to a 2019 study published in the British Journal of Clinical Pharmacology. Even among those aged 50 to 59, the figure was 71 per cent.
Professor Sir Munir Pirmohamed, NHS chair of pharmacogenetics at the University of Liverpool, says 99.9 per cent of the UK population have at least one gene variant that affects how a drug will work for them, and one in four people have four of these variants.
The benefits of testing individuals for such variants were highlighted in the PREPARE trial, published in The Lancet in 2023, which found screening patients for 12 genes – and adjusting medications accordingly – reduced adverse drug reactions by 30 per cent.
‘This type of screening could save the NHS some of the £2.2 billion it spends each year treating adverse drug reactions,’ says Professor Pirmohamed, who points to countries such as Spain, the Netherlands and US ‘which are doing this already, where there is good evidence that it makes a difference to patient lives’.
He adds: ‘And the list of drugs that require genetic testing will grow as evidence builds.’
The feasibility of introducing a nationwide NHS genetic testing service is currently being assessed in the PROGRESS trial, led by the North West Genomic Medicine Service Alliance. Patients in the study are offered a simple blood or saliva test to identify gene variants affecting drug response. The results so far are striking: 28 per cent of patients needed their prescription changed based on their genetic profile.
A second phase is now under way, involving 1,350 patients across the UK. It uses a tool called ProgressRX, which converts genetic data into prescribing advice for GPs.
Professor Pirmohamed says the long-term goal is to have everyone’s genetic profile recorded and available through the NHS app, so doctors and pharmacists can tailor treatment. ‘We want to move towards pre-emptive testing, so it’s there in your GP records,’ he adds.
Professor Yeo believes that within 15 to 20 years genome sequencing at birth could become routine.
Dr Cork says that hundreds of genes can predispose someone to weight gain, each contributing a small but cumulative effect
Such genetic tests are in fact already available on the high street, including Bupa’s My Genomic Test, £225, which analyses DNA responses to more than 100 common medicines, as well as Get Tested (£249.99, gettested.co.uk), which offers a DNA Pharmacogenetics check that covers 50 medicines. The Day Lewis chain offers it at its Stockwell branch in south London for £199, including a consultation.
In the course of writing his book, Professor Barber underwent the test at Day Lewis, which identified 16 drugs he might not respond well to. ‘One was the painkiller codeine. I lacked enough of an enzyme to break it down, so it wouldn’t work for me,’ he says.
‘Another was flecainide. The test revealed I couldn’t break the drug down, so it could quickly reach toxic levels in my body and should be avoided. In fact, I’d been prescribed this drug in the past for an irregular heartbeat, but stopped after one tablet because I felt my heart racing.’
As well as genes, there are many reasons why medication may not work. These include not taking it as directed and interactions with other medications or foods. For example, grapefruit juice can hinder the effectiveness of cholesterol-lowering statins.
Underlying liver or kidney disease can also affect drug effectiveness – both organs are involved in the breakdown and removal of medication from the body, so if they aren’t working effectively then drugs can build up and potentially become toxic.
Professor Barber adds: ‘Your body size can also affect how your medication will work.
‘If you are overweight or obese, some drugs may sit in fat cells and not circulate and work as intended. Meanwhile, if you are small, then the same dose that works for a big rugby player, for instance, may cause you more side-effects as there’s a higher concentration in your blood.’
There is also emerging evidence that the gut microbiome – the community of bacteria and other microbes that play an important role in health – may also affect how drugs are broken down in the body.
‘The microbiome can activate a drug, inactivate it or make it more toxic,’ says Professor Barber.
Indeed, a 2022 study in the journal Microbial Ecology illustrated just how powerful gut bacteria can be. It found the bacterium H.pylori – which an estimated two in five Brits has in their stomachs – could impair absorption and effectiveness of the drug levodopa used for Parkinson’s disease, for example; and E.lenta (thought to be present in 80 per cent of people’s gut) inactivated the drug digoxin, used to treat heart failure.
‘Just as two people can follow the same recipe and get different results because they have different kitchens, our bodies can respond very differently to medicines,’ explains Professor Guirguis.
So what should you do if you don’t think your medication is working?
Professor Barber says with some drugs – such as those for pain or acid reflux – you should know within a few days of taking them, as you would get physical symptom relief. ‘If they aren’t having an effect, go back to your GP – they may try a higher dose or prescribe an alternative.’
For other drugs such as blood pressure pills or statins, you might not feel different. But ‘in these cases, it is worth investing in a blood pressure monitor and having a blood test for cholesterol at least once a year. And with antidepressants you should feel an effect within four weeks – this is one area where pharmacogenetic testing would make it easier,’ he adds.
As for GLP-1s, if you haven’t lost at least 5 per cent of your body weight after taking the full dose for three to six months, you’ll probably need to change the treatment or look to other ways to lose weight, says Alex Miras, a consultant in endocrinology at Imperial College Healthcare NHS Trust in London.
And if you are on long-term medication, your GP should offer you an annual medication review to check symptoms, side-effects and how well a drug is working.
How To Take Drugs, by Professor Nick Barber (Bluebird, £22) is out on Thursday.
