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Dr. David A. Kessler has always been in the business of keeping people healthy – but by his own admission, he hasn’t always applied that to himself.
Kessler’s problem was with food. In medical school, greasy French fries and salted roast beef helped him stay up studying and researching late at night. Over the years, his weight fluctuated. He’d gain 20 or 40 pounds in a relatively short time frame, then slowly lose the weight, usually by going on a low-carb, high-protein diet, and exercising.
He went on to have a long career in public health, including a seven-year tenure as Commissioner of the Food and Drug Administration in the 1990s, where he advocated for better nutrition labels and against the tobacco lobby.
After spending two years stuck at a desk as chief science officer of the White House COVID-19 Response Team, Kessler had gained significant weight. His usual diet and exercise routine didn’t help him shed pounds like it had in the past. Then an endocrinologist asked if he’d like to try one of the new class of glucagon-like peptide-1, or GLP-1, drugs that include Wegovy and Mounjaro.
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He lost about 60 pounds within seven months of starting the injections. Kessler documents his experience in the new book Diet, Drugs, and Dopamine: The New Science of Achieving a Healthy Weight. He also breaks down the science behind obesity, and what makes these drugs so effective.
Here are eight takeaways from our conversation with Kessler about using the GLP-1 drugs, and the changing landscape of weight loss.
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1. Our food environment drives weight gain
Foods high in salt, sugar and fat that are “highly palatable and energy dense” are pretty much everywhere and our brain chemistry drives us to consume them, says Kessler.
“We put [them] on every corner, and we made it available 24/7. We’re living in a food carnival,” he says. “What did we expect to happen?”
Kessler calls these foods “ultra-formulated” (instead of “ultra-processed”) because they’ve been engineered to manipulate the brain’s reward system. They can activate the same reward centers that addictive drugs do. “It’s not willpower,” he says. “It’s biology.”
He says GLP-1 drugs are remarkably effective in countering this pattern. “They have changed the landscape of weight loss,” says Kessler.
And while he’d like to see the “root cause” of obesity and related chronic diseases tackled, he says he’s “not optimistic that we’re going to change the food environment overnight. In the meantime, these are effective tools.”
2. Being overweight isn’t always unhealthy but one kind of fat is
While BMI or body mass index has long been used to measure obesity, Kessler is among a growing number of scientists who say it’s not a helpful indicator of health.
Rather visceral fat, which is found in and around abdominal organs including the stomach, liver and intestines, is the driver of metabolic disease, says Kessler. Visceral fat leeches fatty acids called adipokines or chemokines, which cause systemic inflammation in the body.
“And that inflammatory state results in organ damage that leads to cardiometabolic disease, kidney disease, diabetes, certain forms of cancer, and potentially certain neurodegenerative changes,” says Kessler.
You can get a rough estimate of whether you’re carrying a risky amount of visceral fat by measuring your waist circumference, Kessler says. A circumference greater than 40 inches in men, or 35 in inches in women is a rough indicator. You can also calculate your waist-to-hip ratio.
A body composition scan can offer a more precise measurement.
3. On GLP-1 drugs, get comfortable with being uncomfortable
The great thing about these drugs, says Kessler, is that they allow you to relearn how to eat. But that comes with some caveats.
GLP-1 drugs are powerful appetite suppressants, Kessler says. They increase feelings of satiety, making you feel full after a smaller portion than normal. They do this by slowing down the emptying of the stomach into the small intestine, thus keeping food in the stomach for longer.
This feeling of fullness can be unpleasant. Kessler describes it as being “at the edge of nausea.” He compares it to the way your stomach might feel when you’ve eaten a bit too much at Thanksgiving dinner.
If you push through and keep eating anyway, you might experience GI issues like abdominal pain, diarrhea and vomiting. In the book, Kessler acknowledges that you can’t really separate those unpleasant feelings from the effective mechanism of the drugs themselves.
“There’s great variability,” Kessler says. Some people take the drugs and lose weight with no side effects.
But for most, he says, there’s an element of negative reinforcement. “If you know that if you put anything else in that stomach that’s going to cause distress, you become conditioned to not to put more food in your stomach.” As a result, patients start eating less, he says, and avoiding heavy foods.
At their worst, side effects such as vomiting and nausea or hypoglycemia can land you in the emergency room.
“I don’t think the companies have leveled with the American public on how these drugs work,” says Kessler. They can be a powerful part of a plan to achieve and maintain a healthy weight, he says, but the drugmakers and the FDA should do more to educate consumers about the side effects.
4. Find a good doctor, or better yet, a team
The side effects are one reason it’s important to work with a physician who can monitor your progress and help you find the right drug at the right dose. It could be your general practice doctor or an internist, says Kessler. Working with an obesity medicine specialist, he says, is ideal, though he acknowledges finding one may be a challenge.
And since taking this drug will change your eating habits, Kessler recommends working with a dietician or nutritionist along with a doctor.
With good medical care, he says, many people can still take pleasure in food at those smaller portion sizes.
5. Eat plenty of protein, and fiber
GLP-1 medications don’t change the fundamentals of healthy eating, Kessler writes, and it’s important to be mindful about your food choices on the drugs.
He says if you’re trying to lose weight, with or without drugs, protein is key, because it increases feelings of fullness. And, it can take the place in your meal of some of the bad stuff.
“If you are increasing the protein, you’re decreasing the rapidly absorbable carbohydrates, you’re decreasing fat, excess calories, and sugar,” says Kessler.
And when you are on a GLP-1 drug, he says it’s super important to eat foods high in fiber. Remember, the drugs slow down the emptying of the stomach into the small intestine, and that can lead to things getting backed up further down the line, Kessler says.
“People think constipation is just constipation, but that constipation can turn into intestinal obstruction that can cause perforation and people can die,” says Kessler. “So keeping the GI tract healthy is essential.”
And stay hydrated.
6. Know the risks, including those that aren’t on the label
Kessler worries about people taking the drugs going too far in the other direction – from overeating to malnutrition.
“From what I can tell, many people on these highly effective drugs are eating less than a thousand calories a day, some as low as 600 to 800, and that is a level of semi-starvation,” says Kessler.
Kessler says drugmakers should do more to inform patients about the risks of developing eating disorders, and gastroparesis – a chronic condition where gastric emptying slows down significantly.
It’s also common to lose some muscle mass along with fat while on these drugs, which can be problematic, Kessler writes. One study he cites in the book showed that 40% of the weight loss in patients on once-a-week injections of semaglutide came from lean body mass. And about a third of that was muscle. That’s a reason to keep on top of your nutrition and strength-training while on these drugs, he writes, “especially for older people like me, who are [already] susceptible to muscle loss.”
There are people who should steer clear of GLP-1 drugs, Kessler notes, including those with a personal or familial history of certain thyroid and endocrine cancers, those with chronic kidney disease, pancreatitis, inflammatory bowel diseases, uncontrolled diarrhea or constipation or gastroparesis, or if you are pregnant.
7. Compounded versions of the drugs may be riskier
Kessler says compounded GLP-1s, which are often cheaper than brand-name drugs and can be ordered online, carry additional risks.
“A drug that’s been approved by the brand name manufacturers…There are inspections, there’s standards to make sure what’s in the injectable actually matches what’s on the label. The FDA’s on top of it,” says Kessler.
Whereas in compounded medicines, the active ingredients are manufactured abroad, shipped in bulk, and distributed to compounding pharmacies through middlemen. “I’m not even sure everyone can trace back where the drugs are being made,” he says.
8. When it comes to going off GLP-1s, not much guidance is available
When Kessler reached his personal weight-loss target, he was developing some slight abdominal pains, so he decided to stop.
Once he went off the drug though, Kessler says he was flying blind when it came to maintaining his weight. And he thinks that’s a problem.
“The companies and the FDA, no one’s identified an endgame with these drugs,” Kessler says.
He says there’s very little data on whether or how the dose should be titrated to wean patients off, or how to adjust when your appetite and cravings start to return. In addition to working with your doctor to come off the drug, Kessler recommends a high-protein diet, because protein replicates the feelings of satiety you get from a GLP-1 drug, and may help you to sustain a lower weight.
Since that first seven months, he’s been on and off the drug again.
“But that’s not the way we should be using drugs, flying blind, coming up with our own solutions,” he says. “Companies have to study this. The FDA has to require how to use these drugs safely.”
