Semaglutide is a (mostly) free lunch

Semaglutide and other GLP-1 (and GLP 1 and GLP 2) inhibitors may not be “miracle” drugs, but all the evidence so far suggests that are pretty damn amazing and really life-changing for a substantial number of their users.  That’s good!  What’s kind of amazing, though, is how much some people just seem to want these drugs to actually be bad.  I actually think it’s pretty similar to my “diet soda is a free lunch” theory.  This even came up in a recent episode of Science Vs on these drugs:

WZ Yeah exactly, so all over social media you see a lot of scare mongering about these drugs … but then there’s studies like this!  I mean, that’s that’s huge – less heart attacks!

RR Yeah, the whole thing is a it’s all about the pluses and the minuses, right? Like all medications. And so,Vibha –  who’s the doctor that we talked to earlier in the episode about muscle loss. This is one thing that she and I talked about. And she said that at the end of the day, we know that for a lot of people and a lot of her patients specifically, the pluses here outweigh the minuses.

RR My pet theory is that people are overstating some of these downsides because they’re morally opposed to the medications because it looks like an easy way out, what do you think, do you agree with that?

VS I agree, yknow there are definitely– even amongst my colleagues, physician colleagues, it’s a new concept. These are tools. They’re no magic wand but they’re a beautiful tool and should be used appropriately

I really enjoyed David Wallace-Wells take, “This Is What a Miracle Drug Looks Like, and It Costs Only $5 to Make”

If anything, though, we’ve probably talked too much about cosmetic weight loss and Hollywood vanity — and certainly made too many comparisons to fen-phen, Botox and Viagra. The GLP-1 drugs have been shown to cut risk of heart attacks, strokes and death from coronary disease by 20 percent among overweight and obese patients, presumably through the salubrious effects of weight loss, though the researchers can’t yet say for sure. Semaglutide has been shown to eliminate or reduce the need for insulin among those with recent-onset Type 1 diabetes. In a clinical trial of people with Type 2 diabetes and moderate to severe kidney disease, the drug reduced the risk of kidney disease progression and cut the death rate from cardiovascular and kidney-related causes by 24 percent — such a clear result that the trial was ended early. Semaglutide has reduced fatty liver deposits in patients with H.I.V. and nonalcoholic steatotic liver disease. It has normalized the menstrual cycles of those with polycystic ovary syndrome. (It has also, somewhat mysteriously, seemed to produce a wave of unintended pregnancies among women taking birth control, at least if TikTok videos are to be trusted.)

Studies have shown promise in treating Alzheimer’s and Parkinson’s with GLP-1 drugs, perhaps by regulating insulin levels and reducing inflammation, and the drugs may yet prove useful in treating many other conditions made worse by chronic inflammation. Some studies have found large decreases in the risk of depression and anxiety; others found smaller but still positive effects. There are potential applications for schizophrenia and neurological dysfunction, thanks to the role that insulinlike hormones like GLP-1 play in the development of the central nervous system and the way semaglutide reshapes the brain’s chemical reward system. It seems to bend the curve on alcoholism and drug addiction and curb other addictive behaviors, as well — compulsive shopping and sex addiction, gambling and nail biting, smoking and skin picking. A compulsive nation has stumbled into what looks like a treatment for compulsion and one that happens to protect against some of the country’s biggest killers and curb some of its most pervasive pathologies and inner demons…

Americans love to dream of miracle drugs, but hardly anything ever seems to fill the bill. True, semaglutide has arrived with real questions trailing like bunting: Much of the weight loss is from lean muscle mass, which isn’t ideal, and there are reasons to worry over the possibility of thyroid problems, loss of bone density and sarcopenia, a weakness disorder associated with aging. There are potentially other serious long-term side effects, though millions of Americans have been taking Ozempic for Type 2 diabetes for years without serious issues. (Some of them do report more familiar side effects, like nausea.) The GLP-1 drugs aren’t a permanent fix in a single shot — whether the thing being addressed is body mass index or cardiac risk or the progression of Alzheimer’s — but a permanent disease-management program. They also haven’t exactly cured cancer, although more than a dozen cancers are linked to obesity, and in at least one case, colorectal cancer, there is reason to believe GLP-1 drugs may directly cut the chances of developing the disease.

All that means that semaglutide isn’t exactly a cure-all, in the vernacular sense. But it seems to be about as close as we’ve gotten, even in a time of racing biomedical progress, to that old science-fiction proposition — one pill for almost everything and almost everyone forever.

Yglesias on a piece about the extreme negativity bias in reporting about everything these days:

Something that I do note about the GLP-1 drugs is that the media coverage of them has been oddly negative, almost obsessively focused on downsides, to the point that Rachael Bedard’s piece arguing that actually it’s good that we had a medical breakthrough on a serious problem counts as a contrarian take.

And the excellent piece from Bedard:

Elite media discourse around Ozempic can meaningfully influence public opinion and health-care policy. Right now, the most urgent concern about Ozempic is the fact that everyone who needs and wants it cannot get it. Recently, the state of North Carolina had to rescind its policy of paying for the drugs for people who do not have diabetes — in other words, people prescribed the medications primarily for weight loss — because it could no longer afford the ballooning costs. The drugs can cost up to $16,000 a year (depending on the one prescribed), an out-of-pocket cost few people can bear.

So far, the public discussion of Ozempic’s daunting economics have been consistently fatalistic. At the end of the summer, the columnist Megan McArdle and the physician Leana Wen wrote op-eds in the Washington Post within two months of each other saying the cost benefit for the drugs may not pencil out. Nearly every story I’ve read has used the current access challenges as reason to doubt the drug’s miracle status: If it’s only going to be available to the luckiest few, what makes it any better than Botox? Jia Tolentino, in The New Yorker, wrote, “It is possible to imagine a different universe in which the discovery of semaglutide was an unalloyed good … In the actual universe that we inhabit, the people who most need semaglutide often struggle to get it, and its arrival seems to have prompted less a public consideration of what it means to be fat than a renewed fixation on being thin.”

As long as we talk about these medications primarily as “weight-loss drugs” — as medications that have prompted “a renewed fixation on being thin” — insurance companies and policymakers will remain incentivized to treat them as a luxury good. We’ll never ask the questions that need to be asked: If such a large percentage of the country wants Ozempic, and if we now have good-quality evidence that it helps with a variety of serious conditions beyond diabetes, what is our cutoff for determining who truly needs it? And how do we make it available to them? Price is not an inherent feature of most pharmaceuticals. Ozempic already costs less in other countries, and in the U.S., the president recently took the extraordinary step of lowering drug costs for some of the most commonly prescribed medications by using his executive authority. Ozempic presents a radical opportunity to change the chronic-disease landscape in this country. It may require radical policy to make it accessible, and what that policy looks like is the conversation I want to have.

So, sure, I’m entirely open to the possibility that we may yet discover some real problems with this class of drugs.  But, honestly, at this point, the balance of evidence is definitely closer to the “miracle drug” side of the scale and we should just be honest about that, while admitting we need to remain open to ongoing evidence.