Few products have captured public interest as fast as GLP-1 receptor-agonist weight-loss drugs. But one unforeseen consequence of their popularity has been to create what is, in effect, one of the biggest off-label medical experiments ever. This is the rapid spread of “microdosing”: in other words, of taking less than the recommended amount.
Microdosing has become so popular (one estimate suggests one user in seven has indulged in it) that in America a whole industry has grown up around it. It is offered by big online firms such as Noom and Hims & Hers, is also available at lots of smaller medical spas dotted around the country and, most worryingly, is something people often just try for themselves at home.
Some microdosing is routine. For example many patients start with a small dose and work up to a full one in order to keep side-effects in check. Conversely, those coming off the drugs might be told to step their doses down gradually rather than going “cold turkey”. Where things get trickier is when microdosing itself is the goal: to save on the cost of drugs, for example, or through fear of side-effects.
The problem for professional bodies such as the American Association of Clinical Endocrinology, which issue clinical guidelines, is that evidence microdosing works is largely anecdotal—though a paper published in April suggests responses to the drugs do vary with an individual’s genes. Erring on the side of caution, the association’s current advice is that doctors should stick to Food and Drug Administration-approved dosing guidelines.
Some clinicians nevertheless argue that supervised microdosing can help optimise therapy and remark that some patients—sometimes referred to as “super responders”—do surprisingly well on lower doses. Doctors also say that, having achieved their weight-loss goal, some patients require only a smaller, long-term dose to maintain that loss.
Such supervised microdosing is not a big issue because doctors can monitor their patients’ health and adjust the dose if necessary. But taking medication without such support is often unwise, and the worry is that a lot of microdosers are doing just that. One small survey suggested as many as 55% of them are lone rangers.
The drugs themselves are often sold in devices, called pens, which deliver precise doses as a series of “clicks”. One approach employed by microdosers is to withdraw the drug instead using a syringe. Another is to count the clicks in order to dispense a dose smaller than the manufacturers intended. Neither is ideal. Syringes can contaminate the medication. Click-counting is error-prone. And both may extend a pen’s use beyond its 30-60 day shelf life.
Even if microdosing achieves weight loss or maintains it, it may disappoint those who seek the drugs’ additional benefits, such as to cardiovascular health. The studies which demonstrated such benefits employed full doses, so there is no evidence yet that that lower doses will bring them.
In an ideal world, microdosing’s uncertainties would be resolved by proper trials. The world is far from that. And pharma firms have little motive to pay for research which might show that using less of their product is effective. The speed with which GLP-1 drugs have arrived has been a blessing for many. But those who think they know better than their doctors might be advised to pay attention to that old adage, “when all else fails, read the instructions”.