Weight loss jabs ineffective? It could be in your genes, study suggest

A person's genes could play a role in determining how effective weight-loss jabs are, a new study suggests.

Researchers found variants in a specific gene could also predict whether users are more likely to suffer side effects.

The finding could partially explain why some people lose a significant amount of weight after starting treatment, while others barely see any benefit.

It also shines a light on why some users may be more vulnerable to nausea and vomiting.

Experts said the finding, published in the journal Nature, could one day help doctors deliver precision medicine to help people trying to lose weight.

Weight loss jabs are a class of drugs known as GLP-1 receptor agonists, which work by mimicking the hormone GLP-1 to regulate blood sugar levels and suppress appetite.

The new study examined data from almost 28,000 people registered to the genetics website 23andMe who self-reported data on their use of GLP-1s, including Wegovy and Mounjaro.

Analysis revealed variations in two genes involved with hormones in the gut, which regulate appetite and digestion, could play a role in how these drugs work.

One, the GLP1 receptor variant rs10305420, was associated with a slightly greater decrease in body mass index (BMI) among people taking GLP-1 drugs.

Another, rs1800437 in the gastric inhibitory polypeptide receptor gene, was linked with side effects of nausea and vomiting in people taking tirzepatide, but was not associated with how much weight they lost.

The team, led by academics at 23andMe and The University of Copenhagen, said that these genetic differences may partially account for differences in weight loss.

However, other non-genetic factors such gender, age and which treatment a person takes, also play a role.

'Our study detected a robust genetic association with GLP-1 medication weight loss efficacy and associated side effects,' the authors wrote.

But they stressed that the effect was 'modest' as they called for future studies to explore the role of genetics in these treatments further.

An estimated 2.4 million people are taking weight-loss drugs in the UK but severe rationing by the NHS means the vast majority are currently forced to buy them privately.

Studies show Mounjaro - known as the 'King Kong' of weight loss drugs - can boost patients' health and help them lose up to a fifth of their body weight in a little over a year.

Professor Sir Chris Whitty, chief medical officer for England, last month warned relying on weight-loss drugs to tackle the nation's obesity crisis would be a 'societal failure' and said more must be done to prevent people getting fat in the first place.

His comments appear to put him at odds with the Department of Health and Social Care, which announced in February that GPs will be paid millions of pounds in bonuses for prescribing Mounjaro to their fattest patients.

Health Secretary Wes Streeting has also described the jabs as a 'real game-changer' and vowed to make them available to millions of people on the NHS.

Commenting on the new study, Dr Marie Spreckley, research programme manager at the University of Cambridge, said it 'provides biologically plausible evidence that variation in the drug target itself (GLP1R) and related pathways (GIPR) contributes to inter-individual variability in response.

'However, the magnitude of these genetic effects is small in clinical terms.

'Importantly, non-genetic factors such as sex, drug type, dose, and duration appear to explain a substantially larger proportion of variability.'

Dr Spreckley added: 'In terms of how this fits with the wider evidence, it reinforces that while there is substantial variability in response to GLP-1 therapies, genetics is only one part of a much more complex picture.

'Behavioural, clinical, and treatment-related factors remain the dominant drivers of outcomes.

'Overall, this is an important step towards understanding variability and the potential for future precision approaches, but the effects are modest and the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.'