The Worst Argument Against Ozempic

Unfortunately, being skinny might require effort

GLP-1 receptor agonists (henceforth, GLP-1s) are proving to be miracle drugs, but as with any miracle, they have their doubters. The doubters have developed many arguments against GLP-1s and the arguments vary in sophistication, but they thus far fail to overturn the GLP-1 value proposition. I want to briefly mention what I consider to be the worst argument against GLP-1s, because it is an argument that is both popular and weak.

The arguments that GLP-1s are bad because of a litany of side effects that lack strong empirical support, because they have side effects that are indistinguishable from the effects of weight loss more generally, or because they cause transient delayed gastric emptying (gastroparesis) are among the most common, and they’re unimpressive, but neither is the argument that I consider to be the worst.

The worst genuine argument is one that commonly accompanies this chart:

The Economist, 2023

Care to guess the argument? The Economist put it in words:

A… drawback, however, is that those who start taking [GLP-1s] are likely to depend on them for life. Stop, and the weight piles back on, just as with most conventional diets. In the first year after stopping a 2.4mg dose of semaglutide, people regain two-thirds of the weight they lost. And, as with dieting, some people even put on more weight than they started with.

The argument is that GLP-1s are bad… because you regain weight when you stop them? By the same logic, diet and exercise are bad because, when you cut them out, you’ll also tend to regain weight. Weight rebound after giving up exercise programs and dieting is universal, so to the extent that’s a problem for GLP-1s, why isn’t it also stated as a problem for everything else?

There’s a more sophisticated argument that accepts people who need GLP-1s might need to use them forever in order to maintain their reduced weight, but that this is dangerous for reasons. After all, the proponents of this argument claim, we don’t know about the potential long-term harms of GLP-1s. We know about effects since they’ve been approved (circa 2017) but that’s it, and what if being on them much longer has unexpected side effects?

This argument at least facially makes sense and it’s fine to humor it, but we have to do so in a calibrated way.

What might the long-term harms actually be? No one has provided a mechanism to guide the search and the primary mechanism of GLP-1-induced weight loss (agonism of brainstem GLP-1 neurons involved in appetite) doesn’t seem likely to be directly harmful. Why would the harms have not shown up over the past near-decade of use? They must be so unpredictable as to evade detection over a reasonably long period of time. And most importantly, what’s the counterfactual?

Every other day, a new story comes out about something that GLP-1s help to address, from chronic kidney disease to infertility. Given GLP-1s are so universally helpful, I believe we should update against them being mysteriously harmful. Additionally, we should weight the benefits versus the hypothetical costs. We know the benefits to living a life without obesity are enormous, and if I had to bet, I would say that the people taking GLP-1s for weight management long-term will have longer, happier, healthier lives thanks to these drugs, unless the unexpected happens and there really is a lurking harm to GLP-1s—a harm that has, so far, evaded detection and prediction.

In any case, the argument that GLP-1s are bad because you have to keep using them is hard to distinguish from the argument that exercise and dieting are bad for the same reason. It’s not an argument I humor; it’s the worst genuine argument against GLP-1s.

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