Losing weight with medications like Ozempic, Wegovy, Mounjaro, and Zepbound has revolutionized treatment for obesity, helping thousands shed pounds without surgery. With 70% of Americans overweight or obese, demand for these drugs is soaring, outpacing manufacturing capacity, affecting the nation's economy, and even causing concern among food sellers that the market might shrink due to reduced consumer appetite.
However, the journey to weight loss through these drugs can be challenging. They're expensive, with insurance coverage running about $1,000 per month, and their side effects can be severe, leading to medication discontinuation in some patients. Gastrointestinal woes such as nausea, vomiting, abdominal pain, and, in rare cases, pancreatitis or intestinal obstruction, are potential side effects. In clinical trials, around half of those who started taking the drugs weren't able to complete the study due to these side effects.
Given these challenges, one wonders if people may eventually stop taking these medications or if they become a lifelong commitment for those seeking to maintain their weight loss. A recent study, published Monday in JAMA, adds new details, revealing how people regain weight after stopping Zepbound treatment.
Study on Weight Regain
The study, sponsored by Eli Lilly, who manufactures Zepbound, enrolled 670 obese and overweight adults who successfully lost weight using the drug for nine months. At that point, half of the participants were instructed to continue taking Zepbound, while the other half switched to placebo shots. Neither the researchers nor the participants knew whether they were receiving the active drug or a placebo.
Each participant was encouraged to aim for a 500-calorie daily reduction in their diet and at least 150 minutes of weekly exercise.
Over the following year, those who continued taking Zepbound continued to lose weight and shed an additional 6% on average. However, their weight eventually stabilized, while those who switched to placebo started to gain weight back. Around 9 out of 10 participants who tolerated the highest dose of the medication (15 mg per week) were able to maintain at least 80% of their weight loss compared to 17% of those in the placebo group.
"When you look at the extent of the weight gain, you see that they've regained approximately half of the weight they lost during that year," said the study's lead author, Dr. Louis Aronne of New York City. A specialist in weight loss medicine and professor of metabolism and nutrition at Weill Cornell Medical College.
Zepbound, like Ozempic and Wegovy, mimics the GLP-1 hormone, which lowers blood sugar, slows digestion in the stomach, and reduces appetite in the brain. But it also mimics the GIP hormone and strengthens its effects. In clinical trials, people who tolerated the medication's highest dose (15 mg per week) lost about 20% of their weight after about 1.5 years of use.
Originally, it was approved as a diabetes medication, helping people with Type 2 diabetes control their blood sugar levels. In November, the FDA allowed its sale as an obesity drug through Eli Lilly. When it's used for weight loss, it's sold as Zepbound.
Adults were eligible to participate in the study if they had a BMI of 30 or higher, or a BMI of at least 27 with at least one weight-related health issue like high blood pressure. Participants with diabetes were excluded.
Throughout the study, those taking Zepbound lost an average of 60 pounds and reduced their waist circumference by 9 inches. People who switched to placebo lost an average of 22 pounds compared to their initial weight and still lost more than 3 inches from their waist.
According to Aaron, people who took the placebo were likely to continue gaining weight, although he couldn't say exactly how long that might take.
"There are some glimmers of hope in the data," Aaron said.
Some people who stop taking the medication don't immediately regain the weight they lost, although this isn't always the case. Aron said that approximately one out of every six people can maintain their weight loss without medication.
Aron said they didn't have any information on what helps people maintain their weight loss after stopping the medication, so future research will need to explore this.
Additionally, the improvements in blood pressure, blood sugar, cholesterol, and metabolism remained consistent with their initial levels, even as researchers considered other aspects of their health. However, they didn't surpass their initial results.
"There's no harm in some people saying that they're not any worse than before," Aaron said, "and in some cases, they're much better than before." In some cases, there seems to be a lasting benefit.
Despite the fact that weight loss drugs may lose their effectiveness over time, there are some promising findings. Around one out of ten people who continued taking the medication was unable to maintain at least 80% of their weight loss within a year, meaning they had to start gaining weight again - even while still taking the medication.
Aaron suggested that the body may compensate for the drug's effects over time, as the hunger-suppressing hormone leptin decreases and the hunger-stimulating hormone ghrelin increases.
At this point, a second medication may be necessary.
"Your body is achieving this balance, and when you're trying to manipulate two different areas, you get better results," Aaron said.
"In many respects, the study results are not surprising," said Melanie Jay, director of the Comprehensive Obesity Program at NYU Langone, who was not involved in the study. "Obesity is a chronic condition that cannot be cured by medication."
Jay said most of her patients do not like the idea of taking medication indefinitely. She said she was aware of no studies examining alternative strategies for maintaining weight loss after stopping these medications, although they are needed.
Positively, Jay reported that many patients who use these medications note significant improvements in their health, allowing them to reduce or discontinue other medications for diabetes and high blood pressure.
"Even if they may need to take a medication for weight loss indefinitely, the overall net benefit may be less than if they hadn't started using these medications," Jay said.
