The drugs that are breaking in the Obesity field have stunned researchers
A Revolution in Weight Loss: How Ozempic and Wegovy Are Selling Patients Their Body? A Conversation with Susan Nutter at ObesityWeek 2022
But, the drugs aren’t intended for cosmetic weight loss. Ozempic has been approved for diabetes and Wegovy is for obese people who have risk factors for heart disease, such as high cholesterol or high blood pressure. That’s millions of Americans.
There’s been such an increase in demand that an FDA database lists the medication’s active ingredient, semaglutide, as “currently in shortage.” Its manufacturer, Novo Nordisk, says keeping supplies stable is a priority. The company also markets Ozempic to treat diabetes, which is a lower dose of semaglutide.
The hotel ballroom was full when Susan did not show up. Despite being 10 minutes early, she had to manoeuvre her way to one of the few empty seats near the back. At the ObesityWeek conference in San Diego, California, in November 2022, the audience was waiting to hear the results of a drug trial.
A revolution in weight loss is apparently underway. It started in 2021, when the FDA approved the diabetes drug semaglutide for weight loss. The weekly injectable—sold under the brand name Wegovy—can help users lose 5 to 10 percent of their body weight, leading commentators to describe the drug as both a “medical breakthrough” and a “silver bullet” for obesity. Elon Musk says he’s taking it, Kim Kardashian is rumored to be using it, and everyone from Hollywood to the Hamptons reportedly wants a prescription.
The ability to melt weight away by tweaking biology gives credence to the idea that obesity is a disease. In the past, scientists and the public often thought that those with obesity simply lacked the willpower to lose weight. Most people’s bodies have a natural size that can be hard to change. Richard DiMarchi, the chemist at Indiana University Bloomington, said that the body will defend its weight.
Nutter is concerned that people might start these treatments — whose side effects, such as nausea and vomiting, can be severe — to escape weight stigma, rather than to serve a true health need.
Research questions abound, including who will respond to treatment and whether people will have to take these drugs for life — a huge barrier to access, given that they also carry a hefty price tag: the injections often cost upwards of US$1,000 each month.
Jeffrey Friedman and the Phase III Clinical Trial Investigation of a Drug That Mimicked GIP-Inhibits Insulin, a Key Player in the Discovery of Dietary Weight Loss
Jeffrey Friedman was the person who started today’s success when he was trying to figure out how a certain gene was making mice prone to being obese. Friedman discovered that leptin, a hormone that is produced by fat tissue and makes you feel more full, was due to a faulty gene at Rockefeller University. Giving leptin supplements to mice that lacked it reduced their hunger and body weight.
Scientists were impressed by a phase III clinical trial investigating the new drug semaglutide. Di Marchi says that the molecule acts on the same pathways, but remains active in the body for longer. It is possible that it has better access to brain regions that regulate appetite.
The new drugs are more effective than the previous ones. A landmark clinical trial published in The New England Journal of Medicine in 2021 found that the drug led to a 15% reduction in body weight, on average.
Mller, along with his colleagues DiMarchi and Tschp, knew that GIP stimulates the production ofinsulin based on blood-glucose levels. So they developed molecules that mimicked both hormones. After initial studies demonstrated that activating both the GIP and GLP-1 receptors caused weight loss, pharmaceutical companies created their own molecules achieving the same results, thus confirming that the method worked.
The levels of weight loss are achieved only through bariatric surgery, thanks to the uncertainties. This procedure reduces body weight by 30% or more after six months, and the weight loss continues for the next year or two.
Ruth Gimeno, group vice-president of Diabetes, Obesity, and Cardiometabolic research and early clinical development at Eli Lilly, says she would not have agreed to the surgery if she had known about it a decade ago. The company intends to apply for the drug’s approval when there are results from the second phase III trial.
Mller said that they were the first to come up with the crazy idea. “And we were quite heavily criticized in the field.”
How Affordable is It to Stop Obesity? The Case for Medical Insurance Coverage for Wegovy and Other Weight Loss Drugs
Other approaches include ‘triple agonists’ that mimic the actions of GLP-1, GIP and a third hormone, glucagon, which also stimulates insulin secretion9. Another gut hormones that are involved in appetite is being explored. And some researchers are investigating the monoclonal antibody bimagrumab, which increases muscle mass while decreasing fat.
Another unknown is who will respond to these drugs — and who won’t. Drugs seem to be less effective for weight loss in people with diabetes compared to people without the disease. Conditions such as fatty liver disease and having fat around the organs, known as visceral body fat, might also affect how people respond to different drugs, Tschöp says.
Others worry about the idea that these drugs offer a quick fix. This misconception is a common one among clinicians, says a clinical psychologist at the Cleveland Clinic in Ohio who specializes in behavioral health and body image. “Some people who still hold on to those mistaken beliefs will say, ‘Oh, now people can just take this pill and that’s the easy way out of obesity,’” she says.
But insurance coverage is very spotty. Medicare does not cover Wegovy or other weight loss drugs, and many insurers follow Medicare’s lead. Increasingly, there’s pressure to change this. As STAT reported last week, the Moffitt Cancer Center in Florida is lobbying for legislation that would allow Medicare to pay for obesity drugs, citing the link between obesity and cancer risk. The NAACP is also registered to lobby on this issue.
The OAC wants the pharmaceutical companies to offer affordability programmes. Eli Lilly, for example, has a ‘bridging programme’ for Mounjaro — tirzepatide for type 2 diabetes — under which the medication can cost as little as $25 for the first three months. A similar programme is available for Wegovy.
Studies show that addressing obesity could allow health-care systems to save enormous amounts of money by reducing a slew of conditions linked to the disease.
Many people can’t afford to continue taking their medication for a long period of time because it is out of pocket. And when people stop taking it, there’s often rebound weight gain that’s hard to control. A study showed that most people gain back their weight within a year of stopping the medicine.
The fact that people may need to stay on Wegovy indefinitely has raised concerns about the long term use of the program. GI symptoms are the most common side effect of the drug. “It can be nausea, vomiting, stomachache, or both,” he says.
“It gave me more energy,” she says, allowing her to exercise and do house chores. Her cravings for sugar subsided, and she felt satisfied from smaller meals. Hamilton says that he was surprised at how well he felt. Hamilton says it’s easy to administer the drug at home, because it’s done once a week.
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Blue Cross and Blue Shield of Illinois told NPR that there are different benefits offered by employer plans. “Weight-loss drugs like Wegovy may be covered, depending on the member’s benefit plan,” a spokesperson for the company said. Other insurance carriers consider what employers are willing to cover when deciding on coverage.
“This hormone is telling your brain, I’m full, I don’t need to eat anymore,” explains Dr. Robert Kushner of Northwestern University, who treats Yolanda Hamilton. Kushner also serves on a Novo Nordisk medical advisory board, for which he receives an honoraria.
The pharmaceutical companies have taken natural hormones and made them into drugs. So, it’s not a surprise that when people stop taking the medicine, they start to feel hungrier, he says.
“I want to eat sweet things,” Hamilton says. And her appetite has increased. She doesn’t feel like she is satisfied with small meals anymore. She says that she’s losing her energy when the weight comes back.
Hamilton is being helped in her appeal by the office, but she’s worried that her blood pressure will go up and she may have to stop taking her medication. She is at risk of having these conditions get worse if she regains her weight.
“If I gain more weight, I will be on more medications,” says Hamilton. Given her long struggle with weight loss, she’d finally found something that was working.
Weight Loss Drugs as a Threat to the Obesity Epidemic and Other Health Care Costs: GoodRX vs. BadRX
But, this chart from GoodRX shows the lowest price among all retailers is $1,304 per month for people paying out of pocket, which is out of reach for most people — even with a coupon.
“Some of the people who need it the most are unable to access it,” Robinson says, pointing out that people with low incomes experience obesity at disproportionately higher rates.
In addition, the American Academy of Pediatrics has new guidance recommending that pediatricians offer weight loss drugs to adolescents 12 and older with obesity as an adjunct to behavior change and lifestyle interventions.
Increasing the dose over time can help people tolerate the drug better. The drug is currently being evaluated to see how it affects the cardiovascular system.
The drug has a black box warning as it was found to cause tumors in rodents. So, if a patient has a family history of a particular kind ofthyroid carcinoma or another rare condition, doctors need to check them out to see if it’s related to their other condition. The conversation would be between a patient and his or her doctor. If you have no history of these conditions, “this medication is thought to be safe”, according to him.
This is a reminder of how important it is to fight the obesity epidemic. The risk of tumors in the thyroid may be unnerving. Obesity is a leading cause of death in the U.S., and doctors point to the risks of leaving it unaddressed.
To be honest, exercise and diet modification are still the first things to try. But given that about 70% of Americans are overweight or obese, nearly half of adults in the U.S. have hypertension and more than 1 in 3 have pre-diabetes, doctors’ groups cite an urgent need to layer on more interventions that can be helpful.
“We, as a society, are spending $173 billion in obesity-related health care costs,” says Dr. Marcus Schabacker, CEO of ECRI, an independent, nonprofit group that has reviewed the evidence of new weight loss drugs.
He argues that the drugs can be part of destigmatizing obesity by treating it like any other disease that you treat with medicine. “If someone with hypertension was to just do exercises and change their diet, then they would not be fine.” No, we don’t give themblockers. It’s the same here. Exercise and diet are key components of tackling obesity, but so are medications which have proven to be effective,” he says.
The victorious narratives gilding drugs like Mounjaro are already being positioned as a direct challenge to fat activism. For decades, the movement has pushed for social and economic opportunity for people of all sizes through civil rights, fat pride and liberation, and biomedical evidence itself. Many people are aware that diet andlifestyle changes such as calories restriction and exercise do not work for 97 percent of people, and that many people end up gaining back more weight than they lose. But what happens to the strength of these arguments when a weight loss drug seems to work?
From their inception in the 1950s, operations like gastric bypass (which reroutes food away from the stomach, inducing malabsorption) and gastric sleeve (which involves partially amputating the stomach so it holds less food and produces fewer hunger hormones) have been sold as a potential panacea, says Lisa Du Breuil, a clinical social worker at Massachusetts General Hospital. Only a small number of people who qualify actually go under the knife, but those who do can lose up to 70 percent of their excess weight.