GLP-1 weight loss drugs will not end the worldwide obesity epidemic

As widely expected, Mounjaro gets FDA approval to treat obesity. Crémieux predicts these new weight loss drugs will make obesity a thing of the past:

This seems like a huge leap of faith. This assumes that the drugs work equally well on everyone, which they don’t; are affordable, which they aren’t; and work long-term, which we don’t yet know. It’s not yet known why some people, controlling for dosage and initial BMI, lose much more weight than others. Given how expensive these drugs are and the side effects, it would be useful to be able to predict who stands to benefit the most or the least. As these drugs gain popularity, over the next decade we will have a huge trove of data to answer these questions and more.

The long-term track record for weight loss drugs and procedures is poor. Sometimes the drugs or procedures work well initially, but either slowly stop working (such as weight regain after gastric bypass), and or come with bad side effects (phentermine can lead to addiction and tolerance), or are too expensive. As I discussed earlier, despite hype about people who lose a hundred pounds or more with these new drugs, many plateau after losing only 5-10% of initial body weight, and are still significantly overweight or obese. Others lose even less or nothing at all. Are those people going to keep shelling out $1,000/month to lose so little weight, along with the side effects? Probably not. Survivorship bias means we only hear about the big weight loss success stories, not those who lost much less and who may be less inclined to share.

A 270-pound person who loses 30 lbs, although a good amount of weight, is likely still fat, just not as fat. The usual response is that there are other benefits besides weight loss, such as improved blood markers (e.g. reduced A1C) and less stress on joints. Even so, this seems like goalpost moving. These drugs are specifically billed and marketed as weight loss drugs; that is why there is so much demand and hype in the first place. There is a social element involved: people want to impress their friends and families with their new, slimmer figures, not improved blood tests. If better blood markers is the objective, there are far cheaper alternatives, including even at no cost, such as exercise and cutting out excess salt. The problem is, lifestyle interventions are generally insufficient to produce significant, long-term weight loss for the general population, hence Wegovy.

Josh Barro makes an argument these these drugs have a positive ROI due to saving money and increased worker productivity, but I don’t think this can be taken for granted, especially given that these drugs come with side effects, which can in turn also reduce worker productivity. Also, even if businesses benefit, someone still has to pay, whether it’s consumers, insurers, or governments; it’s not a ‘free lunch’. Drug choices are made at an individual level, even if society collectivity may benefit. I would surmise that nausea and still being fat is not worth the $1,000/month for most people even if collectively society saves money or spends less on obesity-related complications.

I call it the ‘insulin and antibiotics effect’ which is that the efficacy of those things at treating diabetes and infections were low-hanging fruit and set unrealistic expectations for medicine. Now we’re stuck with drugs that do not work nearly as well for everything else, whether it’s cancer, depression, or obesity (although HIV antivirals were a major breakthrough).

The imperviousness of humans to long-term weight loss is one of the most persistently reliable findings in human biology. Losing weight is really hard and uncommon for humans. If you go to the doctor and are overweight or obese, maybe you will be told to ‘eat less and move more’ and given some dietary guidelines. Or if you persist and have good insurance, be prescribed some phentermine or one of those aforementioned GLP-1 drugs. The doctor has more pressing matters to deal with, like people who are sick, not those cannot put the fork down. But if you have unexplained weight loss, the doctor will do a ‘code red’ and run every possible test to find the cause or to rule out anything serious, at no cost to the patient, as weight loss is so uncommon that it necessitates further investigation. The last thing a doctor wants is to send someone home who is losing weight due to an undiagnosed cancer, only to be sued for malpractice later.

There is no evolutionary justification to lose weight, or at least more reasons to gain weight than lose it as far as survival is concerned. Even the most grotesquely morbidly obese still live long enough to reproduce. On Reddit there are probably dozens of dieting subs, each active and full of members, yet only two subs devoted to intentional weight gain (r/gainit and one other I forget).

So to bring this back, GLP-1 drugs have a future–but likely more so for cosmetic reasons–than ending the obesity epidemic. Although some people can lose tremendous weight and be much healthier in the process with these drugs, I predict the biggest customer base will be upper-middle class people who want to lose that stubborn 10 pounds for cosmetic/vanity reasons and can afford to pay out of pocket, or plan to cycle on and off the drug (such as for ‘swimsuit season’). That is still good–10 pounds can make the difference between being overweight or normal weight– but does this justify spending a grand a month? Likely not. And will it solve obesity worldwide? Also likely not.