Over 70% of US adults are overweight, which increases the risk of developing chronic conditions such as type 2 diabetes, heart and liver disease, arthritis, and some cancers.
Weight loss has been shown to reduce this risk. But while the number of people trying to lose weight has increased in recent years, a national study found that two-thirds of those who lose weight quickly regain their 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. Doctors and Surgeons and director. of the Columbia Metabolic and Weight Control Center.
Now, people who are trying to lose weight have a new option – a drug called Wegovy (semaglutide) that is injected under the skin once a week. The drug received FDA approval earlier this summer.
In a 68-week placebo-controlled study of nearly 2,000 participants with a body mass index of at least 27, the semaglutide group had a mean weight loss of almost 15% versus 2.4% in the placebo group. . (Both groups also dieted and exercised.) In comparison, the average weight loss with other drugs is 4% to 11%.
I spoke with Korner to find out more about the new drug and what people should consider 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 medicines that has existed for many years. These drugs mimic GLP-1, a hormone that our body produces when it senses food in the gut, helping the pancreas to produce insulin when glucose is high. GLP-1 receptor agonists were originally developed to treat type 2 diabetes.
It was later discovered that the hormone also slows down gastrointestinal motility, which helps us feel full and acts on the appetite centers in the brain to reduce hunger. It usually takes about 15 minutes for the body to release GLP-1 naturally when you eat. But it can cause a lot of damage in just 15 minutes, before your body has time to release enough hormone to slow down gastrointestinal motility and tell the brain not to eat.
Part of my research at Columbia involves understanding appetite and one way to do that is to measure people’s GLP-1 levels. We found that the levels of this hormone increase after bariatric surgery, which may be one of the reasons why people may eat less food and feel satisfied.
GLP-1 receptor agonists provide a steady supply of this hormone. People who use this type of medicine are able to feel full with smaller portions and are less hungry, which leads to weight loss. The hormone provides a signal that some people do not seem to receive on their own. The reason some people eat more is not because they have less willpower, but because they do not receive a signal that others receive when they eat. We hope that this medicine will provide this signal so that they can eat smaller portions.
How effective is the new drug compared to other weight loss drugs and surgery?
Semaglutide, which can be titrated up to 2.4 mg per injection, has been studied exclusively for weight loss. It was much more effective in terms of the amount of weight loss it produced compared to other drugs currently available in this class. (Another drug called Ozempic contains a lower dose of semaglutide, but has been studied in people with type 2 diabetes.)
In the clinical study conducted by researchers in the United Kingdom, the mean weight loss in the group receiving semaglutide was almost 15%. So, if you have 200 pounds, you might expect to lose 30 pounds.
This drug seems to cause more weight loss than we have seen with any of the currently available weight loss drugs, including drugs that have different mechanisms of action. Perhaps 50% of people taking other weight loss medications will lose 5% of their body weight. In the study, 50% of people treated with semaglutide lost at least 15% of their body weight, compared to 5% of those in the placebo group. This is a huge increase in the number of respondents compared to other weight loss drugs.
With other weight loss drugs, perhaps a third of patients may expect to lose 10% of their body weight. But with the new drug, nearly a third of patients have lost more than 20 percent of their body weight, which is beginning to point to the amount of weight loss we see with some types of bariatric surgery.
We should not expect any medicine to be a magic bullet or that one medicine will work for everyone.
We should also not forget the impact that changing our diet and lifestyle can have. In the study, in which everyone received either the new drug or placebo plus a lifestyle intervention, the placebo group lost 2.4% of their body weight, and their health parameters improved, though not as well. much like 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 about 5% of a person’s initial weight. In this study, too, more than 86% of the participants in the semaglutide group achieved a weight loss of at least 5%.
The study did not include people with diabetes, but did include people with pre-diabetes. A significant number of people who took the drug switched from pre-diabetes to normal blood sugar.
The study also showed that people who were treated with semaglutide had greater reductions in waist circumference and blood pressure compared to the placebo group.
You don’t have to fall into a normal weight category to enjoy the health and quality of life from losing weight. People who are losing weight will see their fatty liver improve, they may no longer have sleep apnea, their diabetes may improve or they may go into remission. They may also see that their arthritis is improving and they will be able to walk and walk more easily. Some people who need knee and hip prostheses but can’t get them because they are too heavy can now qualify, and those who wanted to start an exercise program could now do so.
Should patients who qualify for bariatric surgery try this medicine instead?
If someone is on the verge of qualifying for bariatric surgery, I think it would be worth trying this drug. Even if at some point they will have bariatric surgery, weight loss could help reduce the risk of surgical complications.
If a patient has a very high body mass index, he or she will still be obese if he or she loses 20% of his or her body weight. Even with surgery, many people remain obese or regain some of their weight. So, this medicine could also be used to minimize weight recovery after surgery.
Are there any concerns about the new drug?
Weight loss medications have a history of side effects since the 1950’s. Many weight loss medications have had to be withdrawn from the market due to heart valve disease, pulmonary hypertension and other serious problems. Understandably, some doctors are reluctant to prescribe medications for weight loss because of this sordid past. And many patients know about these past problems with weight loss medications and are afraid to take them.
The safety profile of this drug and this class of drugs is incredibly good and there are no known adverse cardiovascular events associated with them. However, this class of drugs has been associated with rare thyroid cancers in rats. This has not been observed in humans, but as a precaution, the drug is not prescribed to people with a personal or family history of these cancers.
Nausea and, in some cases, vomiting can be a real problem for those taking this medicine; for some, diarrhea or constipation can be a problem. Gastrointestinal symptoms often improve as patients get used to higher doses, so the medicine is slowly titrated over the course of a few weeks. [16 weeks in the trial].
The biggest concern is that some people taking the drug have developed gallstones and pancreatitis, which is a complication of gallstones. This side effect may be due to the drug, but it can also happen when people lose weight fast, because weight loss changes the composition of the contents of the gallbladder and can also change the contractility, creating an environment that is conducive to the development of gallstones.
Some patients may be concerned that they need to inject themselves once a week. But the needle is extremely thin and doesn’t really hurt. The medicine comes pre-filled in a pen – a device that looks like a fat magic marker or cigar. Basically, place the pen on the skin on your abdomen or thigh and press a button until the medicine is released.
Another concern is that not all insurance carriers can cover the new drug. Medicare and Medicaid usually do not cover weight loss drugs, and this drug will cost almost $ 1,300 per month. For most people, it will not be accessible without insurance.
In our weight management clinic, we have patients taking 10 different medications – for diabetes, high blood pressure, arthritis – and using a CPAP device for sleep apnea. Their insurance covers all these medicines and devices. Most plans even cover bariatric surgery. While if you respond to this medicine and lose weight, those conditions may be better controlled and you may not even need bariatric surgery.
Can patients stop taking the medicine after losing weight?
In our clinic, we see obesity as a chronic disease that, for most people, requires lifelong treatment. Studies have shown that most people who stop taking weight loss medications will regain their weight. And the reason is that the drug can provide signals that they do not have on their own, telling them that they are full or satisfying their hunger. If you stop taking the medicine, those signs will go away and the signs of hunger will return, so it will be just as difficult to maintain your weight before taking it.
Some people who take weight loss medications also learn to eat healthier and exercise, and are able to stop medications and maintain weight. However, these patients are in the minority.
If someone has high blood pressure, they are given medication to normalize their blood pressure. Once they reach normal blood pressure, we do not tell them to stop the medicine, because their blood pressure will rise again.
We really need to start looking at weight loss in the same way we do for other diseases. It’s incredibly difficult for patients to come to terms with this – there’s so much stigma, either from the patients themselves or from the health practitioners, because people think that if you eat less and exercise more, you won’t have need treatment.