More than 70% of U.S. adults are carrying extra weight, increasing their risk for chronic conditions such as type 2 diabetes, heart and liver disease, arthritis, and some cancers.
Weight loss has been shown to reduce that risk. But while the number of people trying to lose weight has risen in recent years, one national study has found that two-thirds of those who lose weight rapidly regain the weight.
“Obesity is a heterogeneous disease with many different causes, and what helps one person lose weight may not work well for another person,” says endocrinologist Judith Korner, MD, PhD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and director of the Metabolic and Weight Control Center at Columbia.
Now, people who are trying to lose weight have a new option—a medication called Wegovy (semaglutide) that is injected under the skin once a week. The medication received FDA approval earlier this summer.
In a 68-week placebo-controlled trial of nearly 2,000 participants with a body mass index of at least 27, the semaglutide group had an average weight loss of nearly 15% versus 2.4% in the placebo group. (Both groups also dieted and exercised.) In comparison, average weight loss with other medications is 4% to 11%.
We spoke with Korner to learn more about the new drug and what people should keep in mind if they are considering the drug to help them lose weight.
How does the new drug work?
The new drug, semaglutide, is a GLP-1 receptor agonist. It belongs to a class of drugs that’s been around for quite a number of years. These medications mimic GLP-1, a hormone that our body makes when it senses there is food in the intestine, helping the pancreas make insulin when glucose levels are high. Initially, GLP-1 receptor agonists were developed to treat type 2 diabetes.
It was later found that the hormone also slows down gastrointestinal motility, which helps us feel full, and acts on appetite centers in the brain to decrease hunger. Typically, it takes about 15 minutes for the body to release GLP-1 naturally when you eat. But you can do a lot of damage in just 15 minutes, before your body has time to release enough of the hormone to slow gastrointestinal motility and tell the brain to stop eating.
Part of my research at Columbia involves understanding appetite, and one way we do that is by measuring people’s GLP-1 levels. We have found that levels of this hormone increase after bariatric surgery, which may be one of the reasons people can eat less food and feel satisfied.
GLP-1 receptor agonist medications provide a steady supply of this hormone. People who use this type of medication are able to feel full with smaller portions and they are less hungry, which induces weight loss. The hormone supplies a signal that some people don’t seem to get on their own. The reason why some people eat more isn’t because they have less willpower, it’s because they aren’t getting a signal that other people get when they eat. We hope that the drug will supply this signal so that they can eat smaller portions.
How effective is the new drug compared with other weight loss drugs and surgery?
Semaglutide, which can be titrated up to 2.4 mg per injection, was studied purely for weight loss. It was much more effective in the amount of weight loss it produced compared to other currently available drugs in this class. (Another drug called Ozempic contains a lower dose of semaglutide, but it was studied in people with type 2 diabetes.)
In the clinical trial, led by researchers in the United Kingdom, mean weight loss in the group that received semaglutide was almost 15%. So if you’re 200 pounds, you might expect to lose 30 pounds.
This drug seems to produce more weight loss than we have seen with any of the currently available weight loss drugs—including medications that have different mechanisms of action. Perhaps 50% of people who take other types of weight loss medications will lose 5% of their body weight. In the trial, 50% of people treated with semaglutide lost at least 15% of their body weight, compared with 5% of those in the placebo group. This is a huge increase in the number of responders compared with other weight loss medications.
With other weight loss drugs, perhaps a third of patients might expect to lose 10% of their body weight. But with the new drug, nearly a third of the patients lost more than 20% of their body weight, which is starting to inch towards the amount of weight loss that we see with some types of bariatric surgery.
We shouldn’t expect that any drug is a magic bullet, or that one medication is necessarily going to work for everyone.
We also shouldn’t forget the impact that making dietary and lifestyle changes can have. In the trial, where everyone got either the new drug or placebo plus a lifestyle intervention, the placebo group lost 2.4% of their body weight and their health parameters also improved, though not as much as the semaglutide group.
Can the new drug improve overall health?
For those with a BMI of 25 or higher, clinically significant weight loss—where we really see improvements in health—is around 5% of a person’s starting weight. And in this trial, more than 86% of participants in the semaglutide group achieved a minimum of 5% weight loss.
The trial didn’t include people with diabetes, but it did include people with pre-diabetes. A significant number of people on the medication went from having pre-diabetes to normal blood sugar.
The trial also showed that people who were treated with semaglutide had greater reductions in waist circumference and blood pressure compared with the placebo group.
You don’t have to get into a normal weight category in order to reap the health and quality of life benefits of weight loss. People who lose weight will see their fatty liver improve, they may no longer have sleep apnea, their diabetes can either improve or go into remission. They may also see their arthritis improve and will be able to walk and navigate steps more easily. Some people who need knee and hip replacements but can’t get them because they’re too heavy may now qualify, and those who wanted to start an exercise program may now be able to do so.
Should patients who qualify for bariatric surgery try this drug instead?
If someone is on the borderline of qualifying for bariatric surgery, I think it would be worth trying this medication. Even if they go on to have bariatric surgery at some point, losing weight might help reduce their risk of surgical complications.
If a patient has a really high body mass index, they would still have obesity if they lost 20% of their body weight. Even with surgery, a lot of people remain obese or regain some of the weight. So this medication might also be used to minimize weight regain after surgery.
Are there any concerns with the new drug?
Weight loss medications have a history of side effects, going back to the 1950s. Many weight loss drugs had to be taken off the market because of cardiac valve disease, pulmonary hypertension, and other serious problems. Understandably, some physicians are reluctant to prescribe weight loss medications because of this sordid past. And many patients know about these past problems with weight loss drugs and are scared to take them.
The safety profile of this medication and this class of drugs is incredibly good, and there are no known adverse cardiovascular events associated with them. However, this drug class has been linked to rare thyroid cancers in rats. This hasn’t been observed in humans, but out of precaution, the drug is not prescribed to individuals with a personal or family history of these cancers.
Nausea and, in some cases, vomiting can be a real problem for those taking this drug; for some, diarrhea or constipation can be an issue. Oftentimes, gastrointestinal symptoms improve as patients get used to higher doses, so the medication is titrated slowly over several weeks [16 weeks in the trial].
The biggest adverse event of concern is that some people taking the drug developed gallstones and pancreatitis, which is a complication of gallstones. That side effect may be due to the medication, but it can also happen when people lose weight quickly, because weight loss changes the composition of the contents within the gallbladder and may also change contractility, creating an environment that’s conducive to developing gallstones.
Some patients might be concerned about having to inject themselves once a week. But the needle is extremely thin and it really doesn’t hurt. The medication comes prefilled in a pen—a device that looks like a fat magic marker or a cigar. You basically place the pen against the skin on your abdomen or your thigh and press a button until the medication is released.
Another concern is that not all insurance carriers may cover the new drug. Medicare and Medicaid typically don’t cover weight loss medications, and this drug will cost almost $1,300 a month. For most people, it will not be affordable without insurance.
In our weight management clinic, we have patients who are taking 10 different medications—for diabetes, blood pressure, arthritis—and using a CPAP device for their sleep apnea. Their insurance covers all of those medications and devices. Most plans even cover bariatric surgery. Whereas if they respond to this medication and lose weight, those conditions could be better controlled and they may not even need bariatric surgery.
Can patients stop taking the drug after they lose weight?
In our clinic, we view obesity as a chronic disease that, for most people, requires lifelong treatment. Studies have shown that most people who stop taking weight loss medication will regain the weight. And the reason is that the medication may supply signals that they don’t have on their own, telling them they are full or dampening their hunger. If you stop the medication, those signals will go away and the hunger signals will come back, so it’s going to be just as difficult as it was before the medication to keep the weight off.
Some people who take weight loss medication also learn to eat healthier and exercise, and are able to stop the medication and keep the weight off. However, those patients are in the minority.
If someone has high blood pressure, they’re put on medication to normalize their blood pressure. Once they get to a normal blood pressure, we don’t tell them to stop the medication because the blood pressure’s going to go back up.
We really have to start looking at weight loss treatment the same way we do for other diseases. It’s incredibly difficult for patients to come to terms with that—there is so much stigma, either from the patients themselves or from health care practitioners, because people think that if you just eat less and exercise more, you wouldn’t need treatment.