The following excerpt is from Diet, Drugs, and Dopamine: The New Science of Achieving a Healthy Weight, by David A. Kessler, MD. Listen to David on Food with Mark Bittman here.
The first time I injected myself with a GLP-1 drug, sitting in my endocrinologist’s office in the spring of 2023, the effects kicked in within a few days. I lost my appetite. I also felt bloated. Within twenty-four hours of injecting myself with the next few doses, I experienced intense chills and had to wrap myself in an electric blanket while I worked. I wasn’t ill; it was more like a persistent malaise, a feeling of weakness and discomfort. On more than one occasion, I felt a mysterious, sharp abdominal pain. And then my relationship to food and eating began to change.
A particular moment from my experience stands out to me as emblematic of the key shift that occurs while taking the weight-loss drug. I was having dinner with my family. There was a ricotta-stuffed organic roasted chicken breast with sage and brown butter polenta on the table. Under any other circumstances, I would have happily dug in, and likely would have gone for seconds. But that night, I could hardly eat a bite. I almost had to fake eating altogether, because I was so uninterested in the food sitting in front of me.
I finally felt a freedom from a near-constant yearning, a break from the clamoring “food noise” of daily existence.
It wasn’t just that my appetite was drastically changed. My cravings had changed too. I no longer wanted salt, fat, sugar; I ate simple foods instead. Sometimes, I would take only a little bread with butter. I began eating vegetables on a regular basis for the first time in my life. I finally felt a freedom from a near-constant yearning, a break from the clamoring “food noise” of daily existence.
There is something unique about GLP-1 drugs, something that makes them different from any of the anti-obesity drugs that came before. Dr. John Blundell of the University of Leeds, who has done several studies with the new anti-obesity drugs, explains that they profoundly change how people respond to food. “People don’t stop eating completely,” he tells me. “They still do eat, but they eat small amounts of food, and these small amounts of food now have the same satiating capacity as formerly was the case with a much larger amount of food,” he continues. “The whole system has been amplified, or you can say it’s been curtailed, but these people are now showing a pattern of eating based on small meals with very high satiating capacity. I don’t think you need any specific change in palatability.”
GLP-1 drugs may be teaching us that we should begin to think instead about whether there is an “appetite set point” that can be adjusted using targeted therapies.
When food stays in the stomach longer, satiety signals intensify: You feel full, so you lose the desire to eat more. Dr. Blundell suggests that small meals consumed by people on GLP-1 drugs, which once would have left them unsatisfied, have gained a new ability to suppress hunger. It’s as if the entire system of appetite has been rewired. These smaller meals provide the same level of satisfaction as larger meals used to provide. These results offer a new perspective on the long-running debate about a weight set point. GLP-1 drugs may be teaching us that we should begin to think instead about whether there is an “appetite set point” that can be adjusted using targeted therapies.
The dramatic consequences of taking GLP-1s, including those that I experienced firsthand, made me want to know more about the precise physiological effects of the drugs. At the most general level, the drugs work by reducing caloric intake, the same as diets and bariatric surgery, but the way they accomplish this is totally different. Dr. Blundell and I have discussed whether the changes caused by GLP-1s are due primarily to delayed gastric emptying—the movement of food out of the stomach into the small intestine—leaving the stomach full for a longer period. We know that when food lingers in the stomach, it sends prolonged satiety signals to the brain, but that is unlikely the whole picture.
“There’s no doubt that people still enjoy food, but something fundamental has shifted,” Dr. Blundell says. “When you measure the appetite sensations like hunger, fullness, desire to eat, and so on, they all change. It’s a consequence of feeling satiated, which makes food less attractive. With GLP-1s, because the levels are high twenty-four hours a day, people have this sensation all of the time, feeling full, or fuller, and having no disposition to eat. What GLP-1s do in the long term is decrease any craving for food, to take away that constant feeling that people are stimulated by food, and it increases their sense of control over eating. It allows them to control their hunger drive.”
In personal testimonials, people who take GLP-1 drugs report eating smaller meals with longer intervals between them, suppressing hunger more effectively. Users describe a transformed relationship with food: an indifference, a lack of desire, a state in which food no longer holds its usual allure. It is as if their internal dialog around meals has changed. Evidently, GLP-1 drugs impact both gut and brain mechanisms. They reset how we eat. Food still seems pleasant, but it no longer commands our attention. There is an absence of wanting and craving—at least, while we are taking the drugs.
David A. Kessler, MD, served as chief science officer of the White House COVID-19 Response Team under President Joe Biden and previously served as commissioner of the US Food and Drug Administration under Presidents George H.W. Bush and Bill Clinton. He is the author of the New York Times bestsellers The End of Overeating and Capture and two other books: Fast Carbs, Slow Carbs and A Question of Intent. Dr. Kessler is a pediatrician and has been the dean of the medical schools at Yale and the University of California, San Francisco.
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