“These drugs have the potential to change societies, not just individuals.” — Michael Le Page, New Scientist, March 29, 2025
Obesity is a chronic disease approaching crisis levels. Currently, about 42 percent of Americans are obese, having a Body Mass Index (BMI) of 30 or more, with a predicted rise to 50 percent of the population by 2030. The drugs referred to above — semaglutides — may get us out of the crisis, but with many caveats. In this column and the next, I’ll outline what they are, how they work, and their pros and cons. (BMI is a very rough guide to fitness, good for evaluating populations, not so much for individuals.)
Semaglutides are GLP-1 (glucagon-like peptide 1) receptor agonists, that is, they mimic the body’s natural GLP-1, a hormone released in the small intestine when we eat. GLP-1 has three effects relevant here: It sends a feeling of fullness to the brain; it signals the pancreas to produce more insulin, thus reducing blood glucose; and it prevents the pancreas from releasing glucagon, which normally boosts blood sugar levels. The last two effects are why healthcare providers have been using semaglutides to treat Type-2 diabetes (insulin resistance) for over a decade.
Soon after the Danish pharmaceutical giant Novo Nordisk obtained formal Federal Drug Administration (FDA) approval for their semaglutide Ozempic in 2020 for Type 2 diabetes control, word got out about its off-label effectiveness for losing weight. Seizing the opportunity, the company released a stronger version, Wegovy, specifically for weight loss. The FDA granted Wegovy limited approval for the obesity treatment in 2021, with expanded approval granted last year.
Today, semaglutides are big business. In the U.S., for instance, 1 in 8 adults report their use, with 25,000 people each week starting on them. Last year Ozempic was the eighth best selling drug globally with sales worth $17 billion. While Ozempic and Wegovy (with $9 billion in sales) are the best-known weight loss drugs, there are many others, including Zepbound, Saxenda, Victoza and Monjaro. All require weekly injections, since the molecules involved are too large to enter the body via the digestive tract. However, daily oral (tablet) versions using smaller molecules, including Novo Nordisk’s own Rybelsus, will probably supersede injectables as the popularity of the drugs rises.
A few years ago, the standard intervention for severe obesity was bariatric surgery, which involves removing or tying off part of the stomach, leading to smaller meals as the body adjusts to a smaller stomach capacity. It’s expensive — on the order of $25,000 — and while it leads to weight loss for most patients, the chronic desire for food (“food noise”) doesn’t go away. Some bariatric patients manage to regain their original weight loss, so powerful is the brain’s “hunger” message honed eons ago on the African savannah. Semaglutides seem to bypass the food noise syndrome, sending the message to the brain (probably via our twin vagus nerves and hypothalamus), “I’m sated; I’m not hungry.”
This country still has to come to terms with switching from an attitude of, “Obesity is a personal choice” (so fat people can only blame themselves for their weight) to “Obesity is a chronic disease” (and therefore is a guilt-free candidate for treatment using drugs). In 1942, the World Health Organization declared obesity a disease but it wasn’t until 2014 that the American Medical Association followed suit. Compared to other medical conditions, obesity has gotten a bad rap. While there’s no stigma attached to treating such chronic problems as high blood pressure with ACE inhibitors, arthritis with NSAIDs or depression with SSRIs, obesity is often seen in a different light. “If you’d just eat less and exercise, you wouldn’t be fat,” is a common refrain. Our genetic survival legacy from prehistoric times, on the other hand, says, “To survive, eat as much as you can whenever you can.”
With luck and time, I predict that semaglutides will change societal attitudes towards obesity.
Barry Evans (he/him, barryevans9@yahoo.com, planethumboldt.substack.com) has struggled to overcome his childhood message that obesity is a moral failure. BTW, he’s not a doctor (duh!).
This article appears in The Man Who Unsolved a Murder.