Tirzepatide is one such drug that has recently gained attention. In the experiment, participants who were obese lost more than 20% of their body weight—on average, 52 pounds per person—according to research published in June in The New England Journal of Medicine.
Ania Jastreboff, MD, Ph.D., a Yale Management adult, a pediatric endocrinologist, and a nationally renowned authority on obesity medicine, says of the results: “These results represent a significant step forward in possibly increasing effective therapy choices for persons with obesity.”
Semaglutide is a weight-loss drug administered once a week by self-injection under the skin and is only available with a prescription under the trade name WegovyTM. In June 2021, the FDA authorized it to manage overweight and obesity (with similar medications being developed as well). Although liraglutide doesn’t always work, when it does, it can help someone lose 15% of their body weight. (For instance, if you weigh 200 pounds, that would be 30 pounds.)
Dr. Jastreboff explains that this medication “helps you feel full earlier.” It implies you won’t be tempted to have “seconds” or a snack later.
There are several anti-obesity drugs in use today, and many have been around for decades. However, semaglutide is the first in a brand-new, incredibly potent class of hormone-based obesity drugs. A hormone termed glucagon-like peptide-1 (GLP-1) that targets receptors throughout the body, including the brain, is imitated by semaglutide. GLP-1 is released in the stomach. According to Dr. Jastreboff, GLP-1 tells the brain when a person has finished eating.
The process by which stomach contents are transferred into the first portion of the small intestine as part of the digestion process is known as “gastric emptying,” and semaglutide slows it down. But over time, this impact diminishes, according to Dr. Jastreboff. Semaglutide acts on the brain, which is how it mainly treats obesity.
However, the medication—and its class of drugs—are not novel; type 2 diabetes has been treated with this family of GLP-1 analog medications for over 15 years (semaglutide. primiarly was FDA-approved in 2017 for diabetes). Compared to individuals without type 2 diabetes, those with the illness release less GLP-1 in response to food. According to specialists, that holds for obese persons as well, Dr. Jastreboff said. Semaglutide increases GLP-1 intake for patients, although in a synthetic form, “she claims. “Essentially, they are regaining more of that hormone, which makes them feel satisfied.
The drug seems to be effective for a lot of folks. More than a third of the individuals in a clinical study, many of whom weighed more than 200 pounds, dropped 20% of their body weight in addition to the 12.5% mean weight decrease over the placebo group, according to data that was published in The New England Journal of Medicine.
Dr. Jastreboff and her associates joined us for a meal. They responded to frequently asked queries on anti-obesity drugs.
Do drugs to treat obesity honestly work?
A 49-year-old woman of three who had a full-time job and participated in Dr. Jastreboff’s study underwent weekly injections as part of a clinical trial at Yale to examine tirzepatide. This medication combines GLP-1 with another hormone known as glucose-dependent insulinotropic peptide (GIP). The site’s chief investigator was Dr. Jastreboff.
To remove the additional weight she had carried for years, the participant attempted several diets and exercise regimens, but nothing worked. Despite her best efforts to maintain a healthy lifestyle, she put on 25 pounds while working from home during the epidemic. But I’ve carried the rest of it my entire life, she claims.
She didn’t initially know if she was taking the medication because it was a double-blind experiment in which some participants received a placebo; nonetheless, over a year, she claims that “the weight slid off of me.” She dropped 85 pounds after the experiment, leading her to assume that she was taking the medication.
“It worked for me because my problem is mindless overeating. It has been a major change in my eating habits because the medicine frequently causes me to feel full after only a few nibbles,” the participant adds. She used to “easily” ingest 3,000 calories daily, but throughout the study, she has been unable to consume more than 1,500. Three Oreo cookies make up one dish, and she said it was difficult to stop at three. “I found it a great challenge to eat more than three during the experiment.”
The clinical director of the Metabolic Health & Weight Loss Program at Yale Medicine, a gastroenterologist who has given semaglutide, says: “These medications [such semaglutide and tirzepatide] have the potential to treat many more individuals.” He points out that the drug’s results—15% to 20% weight reduction—are significant because they represent a pattern in which anti-obesity drugs are beginning to approach the 25% to 30% weight loss level, which has so far only been attained with bariatric surgery.
Although some people achieve their plateau quicker, the medication might take more than a year to work to its full potential. Dr. Viana notes that with any anti-obesity drug, doctors like to see a benchmark of 5% total body weight loss in the first three months since this is a solid indicator of whether the drug will continue to function.
What adverse effects may anti-obesity drugs have?
Semaglutide’s side effects were tracked during the studies that led to the FDA’s clearance. According to Dr. Viana, the most frequent adverse effects of semaglutide are gastrointestinal, which frequently include nausea. As the dose increases, “you evaluate how the patient feels, and you may always go back to a lesser one,” the doctor advises.
The participant in Dr. Jastreboff’s tripeptide research study had stomach issues, mild tiredness, and trouble staying hydrated. Still, she believed these side effects were insignificant in comparison to the consequences and adverse effects of obesity.
When she was big, her joints hurt, she had trouble fitting into her clothes, and she felt ashamed to go out in public. We all agree that aircraft seats are growing more minor. Still, that reasoning is useless when attempting to squeeze between the arms and have to buckle your seatbelt all the way.
Scientists are still studying anti-obesity therapies, and they will continue to do so for any medications still in the clinical trial stage.
Meanwhile, doctors say patients will need to take the medications for years—and probably for life—to avoid returning the weight. “We talk about diabetes remission, and, in the same way, patients have obesity remission,” Dr. Jastreboff says.
“Patients are not ‘cured’ once they lose the weight,” Dr. Jastreboff adds. “They need to continue treatment with anti-obesity medications to maintain the weight they lost, just as they would need to continue taking diabetes medication to maintain blood sugar levels.”
Are anti-obesity drugs available to everyone?
Older drugs that were FDA-approved and also had a brain focus are still prescribed by doctors. These drugs can aid patients in losing 5% to 10% of their body weight, which can lower the risk of cardiovascular disease in individuals who are obese or overweight. Older anti-obesity drugs include those that must be taken once daily or more; one calls for daily injections.
However, not everyone qualifies for semaglutide therapy. Adults with obesity, defined as a body mass index (BMI) more significant than 30, or overweight, expressed as a BMI greater than 27 and accompanied by weight-related health issues such as high blood pressure, type 2 diabetes, or high cholesterol, may be prescribed it by a doctor. (BMI is a measurement used to categorize weight. On its website, the Centers for Disease Control and Prevention [CDC] offers BMI calculators.) Medicine is not advised for people with a personal or family history of specific thyroid or endocrine cancers, notably medullary thyroid cancer.
Another warning is that not everyone will respond; according to Dr. Jastreboff, 13% of obese people who participated in semaglutide clinical studies didn’t lose any weight. She believes that’s not surprising because there are several varieties of obesity. Said, “We don’t yet know what they are.”
As with cancer or other diseases, subtyping obesity using biomarkers is not yet possible, according to Dr. Jastreboff. No blood tests can predict how someone would react to a particular treatment or drug, such as a GLP-1 analog like semaglutide.
Before doctors can determine the optimal treatment plan for a particular patient, researchers need to study more about the many subtypes of obesity, she continues.
Will I have to “try and error” until I find the perfect anti-obesity drug?
Doctors collect data on variables like a patient’s eating habits and other aspects till they know more. The ideal prescription for you could also need some “trial and error,” according to Dr. Viana.
But informed decisions are also a possibility. For instance, an older-generation drug called bupropion, also an antidepressant, may be helpful for someone with a history of depression which appears to be overeating to cope (brand names include WellbutrinTM and ZybanTM). This drug is typically combined with a drug called naltrexone (ContraveTM). “We could be targeting the mechanism that’s most responsible for that patient’s fat by employing that pill or combination of meds,” he claims.
Dr. Viana suggests utilizing multiple drugs or combining medication with another intervention for people who wish to lose weight even more and further eliminate symptoms like gastric reflux.
All anti-obesity drugs are provided with a lifestyle approach that covers nutrition and exercise. The endoscopic sleeve gastroplasty, a minimally invasive surgery designed to reduce the size of the stomach, is one endoscopic operation that Dr. Viana has paired with drug therapy. According to Dr. Viana, after that surgery, patients might drop up to 15% of their body weight before reaching a plateau. He advises that you can add a prescription that will help you lose additional weight if you hit a plateau and your personal goal hasn’t been met.
What do you want to achieve with treatment—weight loss or improved health?
Although Dr. Jastreboff stresses that the purpose of treating obesity is not about attaining a specific size—it is about health, losing weight can enhance one’s sense of self and mood.
She notes that therapy with anti-obesity drugs is to “reset the set point,” a phrase used to describe a weight range that the body seeks to maintain and that is increased in the context of obesity. Dr. Jastreboff explains, “If you lose weight by limiting calories, your body feels starving, which encourages a person to keep eating to maintain the raised set point. Anti-obesity drugs function in the brain to assist lower that set point, helping people reduce weight while keeping it off for the longer term.
Anti-obesity drugs may also assist with other weight-related medical issues, such as lowering blood pressure or cholesterol, enhancing blood sugar control in diabetic patients, or delaying the onset of type 2 diabetes, depending on the patient and their other illnesses. In those with type 2 diabetes, the family of GLP-1 analog drugs has also been proven to reduce the frequency of recurrent heart attacks and strokes.
Will the use of these medications eventually alter how people see obesity?
The physicians hope that by educating people about how obesity’s pathophysiology may be treated with medicine, they will dispel the widespread belief that people should be able to manage their disease independently.
“If I can will myself to not be hungry, to not have cravings, to control what I eat every second of every day, I will lose the weight and keep it off,” individuals often believe, according to Dr. Jastreboff, “that’s like saying ‘If I focus hard enough, my blood sugar levels will become normal. She continues by saying that people need to be aware of the physiological explanations for why such a tactic fails. “We can treat obesity with targeted therapy focused on the biology since it is a complicated metabolic illness with a definite biological foundation.”
However, more must be done before more medical professionals, patients, and insurance companies consider obesity a condition.
According to Dr. Jastreboff’s research subject from the tripeptide trial, semaglutide is an expensive medication that is currently not always covered by insurance, and tripeptide is not accessible outside the trial. I’ll probably take medicine for the rest of my life since, according to the studies, you gain weight back when you stop taking the drug. “However, how will insurance work in this scenario? One reason it’s crucial to start viewing this as a medical issue, not a personal one, is that it has to be accessible to everyone who needs it.