“RESIST SAYING, ‘this will be no panacea’. When you find something that is a panacea, that will indeed be news.” This wise advice once appeared in The Economist’s Style Guide, and the first part is routinely enforced. Some people are, however, asking whether the second part’s time may perhaps have come, as a group of drugs now routinely prescribed for type 2 diabetes and obesity are being sought out by healthy people in the hope that they will help preserve that health for longer, and even extend life.
The drugs in question are glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the best known of which is semaglutide (sold commercially as Ozempic and Wegovy). They are already being investigated, with variable success, for everything from Alzheimer’s disease (for which a pair of recent studies showed no positive effect) and Parkinson’s disease to heart failure, drug and alcohol addiction and even arthritis (because weight loss reduces joint strain). But what excites enthusiasts is the idea that they might attack the roots of ageing itself.
Studies of how people age have identified a dozen or so distinct (though interlinked) “hallmarks” of the process—harmful phenomena that affect a wide range of tissues and get worse as the years roll by. Preliminary work, mostly on animals and cell cultures, but also including studies of people taking GLP-1 RAs on prescription, suggests the drugs ameliorate several of these hallmarks.
Top of the list is “inflammaging”, the chronic rise in low-level inflammation which people experience as they get older. GLP-1 RAs seem to inhibit this in several ways, including stopping the formation of protein complexes that trigger inflammatory responses. They also promote the recycling of failing cellular machinery: worn-out mitochondria (a cell’s power packs) and misfolded proteins. This keeps cells ticking over for longer. They help, too, to modulate biochemical pathways that sense the presence of nutrients and orchestrate appropriate responses—the breakdown of which is yet another hallmark of ageing. And they promote proliferation of the type of stem cells that repopulate tissues with new, functional cells.
On top of these promising individual effects, an experiment on mice suggests that GLP-1 RAs may, indeed, extend “healthspan”—the fraction of an animal’s life during which it remains in good nick. It did not, however, demonstrate any extension of lifespan. Nor is preliminary work of this sort the same as proper clinical trials. But that has not stopped many people from jumping the gun by seeking out friendly doctors to prescribe the drugs “off-label”.
On the face of it, this sounds risky. Treating diabetes and obesity, and thus balancing efficacy against side-effects such as pancreatitis, is one thing. Healthy individuals taking GLP-1 RAs for a lifetime, even in small doses, is another. Many users are aware of this, however, and in the absence of the sort of top-down monitoring that would happen in an organised trial have banded together in internet forums to monitor each other and pass around tips.
This is, indeed, part of a wider trend of mutual support at the fringes of pharmacology, with similar user groups forming to monitor off-label use of other peptide drugs and thus, in effect, running informal, uncontrolled trials. Whether those now taking GLP-1 RAs prophylactically will live to regret doing that or, conversely, will live long enough not to, remains to be seen. ■
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