Is there anything GLP-1 analogues can’t do?
It’s probably no exaggeration at this point to say that semaglutide and other GLP-1 receptor agonists are more popular than Jesus Christ.
With this influencer-assisted popularity comes a sense that the T2DM/weight loss miracle drugs are a bit too good to be true. We’re trained to expect that nothing good in medicine comes without a very solid downside, and while there are undoubtedly side effects to semaglutide, they do not seem sufficiently biblical to make up for just how useful the drugs seem to be in curbing the world’s growing problem with obesity.
Anecdotally we’ve heard that users and prescribers are “waiting for the other shoe to drop”.
Well, this is not that shoe. If we credit this new Irish study published in Obesity – small and uncontrolled as it is – the news about GLP-1RAs just got even better.
The team set out to investigate the effects of the drugs on immune function, whose depletion in obesity puts people at higher risk of cancer mortality as well as chronic conditions like cardiovascular disease and poor outcomes in acute infections.
Specifically they looked at natural killer cells, which in obesity lose their ability to produce cytokines and their cytotoxicity, thanks to poor cellular metabolism.
They took 20 people with obesity (mean BMI 46.6) who were about to initiate semaglutide for weight loss and had no history of diabetes or use of immunomodulatory drugs. Using cell culture, flow cytometry and other tricks, they compared NK cell frequency, cytokine production, cytotoxicity before and after six months of weekly injections.
GLP-1 therapy did not restore the frequency of NK cells, but it did restore their interferon-gamma production (by increasing the activity or expression of mTOR, amino acid transporter CD98 and hexokinase-2, for those playing at home).
Interestingly this effect was independent of weight loss. There was reduced BMI and better glycaemic control across the group after six months, but only nine of the 20 achieve clinically significant weight loss, and the two effects were not associated. The team has previously found GLP-1 therapy decreases overall inflammation, again independently of weight loss.
Also interestingly, previous research suggests NK cells don’t have GLP-1 receptors to … agonise? … meaning some other receptor is involved.
All of which will do nothing to hurt sales of Ozempic, Wegovy et al. – good luck to all those waiting for supplies to return to Australia.
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