New study discovers hidden reason why Ozempic might not work for some people
GLP-1 medications like Ozempic aren't everyone's cup of tea - and according to a new study, they don't work for everyone either.
Some people have enjoyed incredible success after using weight loss jabs to help them shed the pounds, while others haven't got the results they set out to achieve.
It turns out that there is a reason why the effectiveness of these drugs varies for person to person, and scientists at Stanford Medicine say it's all to do with genetics.
Researchers spent several years digging into this phenomenon and sought advice from boffins across the globe as they were so surprised by the results of their study.
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The decade-long analysis - which involved experiments on humans and mice, as well as analysis of diabetes drug trial data - was published in Genome Medicine in April this year.
Given that millions of people are now using weight loss drugs such as Ozempic, Wegovy and Mounjaro, scientists have been spending a lot of time trying to understand the potential implications of taking them.
Researchers recently made a 'remarkable' discovery about a beneficial side-effect they can have, while jabs packed with 'triple the strength' have just been approved by the NHS.
But some people who have placed their faith in weight loss jabs have been left disappointed by the efficacy of them. According to scientists at Stanford, their genetic makeup is to blame.
The research team found that patients who have certain genetic variants - which around 10 percent of the population are believed to carry - don't reap the benefits of taking the diabetes drugs.
The variants 'cause a surprising and still mysterious phenomenon that researchers refer to as GLP-1 resistance, in which levels of the hormone GLP-1 (glucagon-like peptide-1), which helps regulate blood sugar, are higher but less biologically effective', the experts said.
"It’s not clear whether the variants affect weight loss from these drugs, such as Ozempic and Wegovy, which are increasingly prescribed to treat obesity," it added.
"They are typically taken at higher doses for weight loss than for diabetes."
The research
The study, which focused on blood sugar regulation, found that people with these variants weren't able to lower their blood glucose levels as effectively as those without them.
Experts looked into two genetic variants that handicap a 'truly fascinating' enzyme known as PAM (peptidyl-glycine alpha-amidating monooxygenase).
PAM activates a host of hormones in the body, including GLP-1, and is 'capable of a chemical process called amidation, which increases the half-life or the potency of biologically active peptides'.
One of the lead author's of the research, Dr Anna Gloyn, said: "We thought, if you have a problem with this enzyme, there’s going to be multiple aspects of your biology that are not working properly."
PAM variants are often present in people with diabetes and they impair their insulin release, so the researchers sought to find out if this 'genetic glitch' also affects the GLP-1 hormone.
For the study, adults with and without a PAM variant known as p.S539W drank a sugary solution and measured their blood every five minutes for the next four hours.
It yielded the 'opposite' of what they imagined, Dr Gloyn, a professor of pediatrics and of genetics said, as patients actually had increased levels of GLP-1 in their system.
"Despite people with the PAM variant having higher circulating levels of GLP-1, we saw no evidence of higher biological activity," she said. "They were not reducing their blood sugar levels more quickly. More GLP-1 was needed to have the same biological effect, meaning they were resistant to GLP-1."
Various other trails also left the Stanford team sure that this phenomenon is 'specific to medications that are working through GLP-1 receptor pharmacology'.
Dr Gloyn reckons that further investigation into how genetics influence various responses to GLP-1 receptor agonists should be conducted, to help further 'explain poor responders' to the medications.
She said experts have still not been able 'to nail' precisely why people with these genetic variants are resistant, adding: "That is the million-dollar question."
Olivia Burke