Sonya Collins
Corena Hughes, a 45-year-old veterinary technician, weighed in at 215 pounds when she decided she had to try something different.
It had been easier to lose weight with diet and exercise when she was in her 20s and 30s. It also didn’t hurt that at that time she had lived in places like Honolulu and San Diego, where she felt motivated to get outside and move. Now Hughes was over 40 and living in Richmond, Maine, a region with long winters and short days. She was battling depression after a recent divorce and hormonal changes brought on by a hysterectomy and hypothyroidism. Her need to lose weight was made more urgent by her rising BP.
But, she said, “I just couldn’t shed a pound. So, at my next physical exam, I said, ‘Doctor, I need some sort of help.’” Hughes knew what kind of help she wanted; she had seen it on TikTok. It was an injectable drug called semaglutide (Wegovy), and her physician prescribed it.
Hughes began shedding weight at a clip of 1 to 4 pounds a week. Within a year, she had lost 30% of her body weight. She last weighed in at about 150 pounds. Her BMI had plummeted by 10 points, from “obese” to “normal.” These results surpass even the expectations set by the literature.
“After the first week, I thought, ‘What is this magic?’” she said.
In a landmark study published March 18, 2021, in NEJM, 1,961 adults with a BMI of 30 or greater and without diabetes were randomized to 68 weeks of once-weekly S.C. semaglutide at a dose of 2.4 mg or a placebo, plus lifestyle intervention. Those in the semaglutide group lost an average of 15% of their body weight compared to a loss of 2.4% in the placebo group. Additional studies published since then have had similar results.
Like Hughes, the public is seeing these dramatic results on social media, in magazines, and on TV and movie screens. Semaglutide prescriptions have increased 40-fold over the last 5 years, according to an analysis by Epic Research which was shared exclusively with CNN. About 1 in 60 Americans were prescribed the drug in 2023.
GLP-1 receptor agonists such as semaglutide may indeed be the “magic” weight loss drug that undoubtedly many people with overweight or obesity—which amount to two-thirds of American adults—have dreamt of. If so, they could bring dramatic population health benefits—at least to the segment of the population who can afford it. Others may take big risks to find an alternative that fits within their budget.
The rich get thinner, the poor stay sick
As GLP-1 agonist makers such as Novo Nordisk and others rake in money and the stock market braces itself against the aftershock, many people who could benefit from the drug cannot afford it. People with lower incomes are typically more likely to have overweight or obesity than their wealthier counterparts, and they are harder hit by the subsequent chronic conditions as well. Increasing use of weight loss injectables among those who can afford them could substantially increase health disparities between the haves and have-nots over time.
Growing use of these drugs has also pushed them into worldwide shortage. Many who find the price of the brand-name drugs out of reach or simply don’t want to pay the high price have turned to compounded versions.
Hughes’ insurance covered 6 months of Wegovy. After that, her cost would have been $1,400 per month. At that price, she couldn’t even afford to titrate down slowly as her physician recommended, so she quit cold turkey.
“I went from being perfectly satisfied eating a pickle and a few olives for dinner to suddenly wanting to eat my arm off,” she said.
Hughes immediately sought out a cheaper compounded semaglutide so she could get her weight management back on track.
Hughes gets the drug for a few hundred dollars a month rather than over a thousand. She’s experienced no adverse events and has faced the same GI adverse effects that are expected with the branded drugs.
The most common adverse effects of GLP-1 receptor agonists are nausea and constipation. There have been some reports of acute pancreatitis, which is believed to be a result of the drug ramping up insulin secretion by the pancreas. Previous concerns about the risk of suicidal ideation were recently called into question by a large retrospective cohort study of EHRs published January 5, 2024, in Nature Medicine that found no correlation between these weight-loss drugs and suicidal thoughts.
Desperate measures
Saving money with compounded semaglutide may come at a high price.
FDA has received adverse event reports after patients used compounded semaglutide. In 2023, United States poison control centers fielded some 3,000 calls about semaglutide—a 1,500% increase since 2019. It’s suspected that patients may be accidentally overdosing on compounded versions of the drug, which they must measure themselves as opposed to the branded medications that come in pre-measured pens.
“What we’ve noticed at the New Mexico Poison and Drug Information Center is that patients are having symptoms consistent with the adverse effects of a normal therapeutic dose, but more severe vomiting and nausea so bad that some patients aren’t able to eat or drink for a few days. That’s when they consider going to the emergency department to get help,” said Joseph Lambson, PharmD, DABAT, director of the University of New Mexico Health Poison Center.
FDA has also issued warnings about some compounders using salt forms of the drug, which is different from the FDA-approved medication. In addition, FDA alongside other agencies worldwide recently sounded alarm bells when counterfeit semaglutide made its way onto pharmacy shelves.
The risks of compounded GLP-1 agonists may increase as the sources of it do.
“There’ve been reports of people going to med spas and getting it,” said Jennifer Clements, PharmD, a clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy. “People are doing this because they want the product, but can’t afford it.”
Pharmacists should seize opportunities, she said, to counsel patients seeking compounded semaglutide on the importance of getting it from an accredited compounding pharmacy.
But while educating patients on where to source compounded drugs could help them avoid adverse events, it doesn’t solve the problem, Clements said.
“The reason we see people pay so much, or try to save money by going through a back door, is because payers are not covering these medications,” she said. “Obesity is not a cosmetic condition. It’s a chronic condition that affects so many other aspects of health and can lead to further complications. People need that medicine to help them because they have tried other things and have not been successful.”
In concert with lifestyle changes
Patients who have only had success losing weight on GLP-1 agonists may expect to stay on them for life, said Daniela Hurtado, MD, PhD, an endocrinologist whose research examines the brain’s regulation of food intake and the benefits of semaglutide.
“The understanding that we have is that in order to maintain the weight loss and treat this chronic disease effectively, there is a very high likelihood that patients will need to stay on the drug long-term. We are treating obesity as a disease, like any other disease such as diabetes or high BP. Once we start an intervention, the plan will be to be on it long-term.” Hurtado sees patients in Mayo Clinic’s Precision Medicine for Obesity program in Jacksonville, FL.
But long-term use of weight loss drugs does not negate the need for lifestyle changes. While patients may lose significant amounts of weight on GLP-1 receptor agonists without making other lifestyle changes, they should be reminded that good nutrition and physical activity are critical to optimum health, not just optimum weight.
In addition to counseling patients on the GI adverse effects and how to administer the drugs, “pharmacists need to tack on that they still have to make lifestyle modifications—changes in what they eat and drink and to be active—because that’s part of weight loss,” said Clements. She added that it’s unclear whether some of the GI distress patients feel on GLP-1 agonists is from the drug itself or from continuing to eat unhealthy foods.
Eat less, feel fuller longer
GLP-1 receptor agonists such as semaglutide entered the market as diabetes medications, but it was soon clear that this powerful medication did more than stimulate insulin production.
“We also found that it can act at the level of the brain to suppress appetite and at the level of the stomach to delay how fast food is emptied from it. So it not only decreases the hunger sensation and appetite, but also gives you a sensation of fullness, or satiety, for a longer period of time,” said Hurtado.
Hughes said the drug not only killed her appetite almost completely, but it also put her off what she considered her Achilles heel when it came to weight management: red wine. “It was my weakness and the culprit of all my weight gain. I would just drop bottles of red wine like it was nothing. And now, I can’t. I don’t like it.”
Hughes’ experience is borne out in preliminary research, too, which suggests semaglutide may help reduce alcohol consumption and curb other addictive behaviors.
David Soliman, a 43-year-old financial adviser in New Orleans, described the appetite suppression he got from tirzepatide (Mounjaro, Zepbound) as a silencing of “food noise.”
“I had to be munching on something or thinking about my next meal all the time,” he said. “It was really remarkable—just kind of like a switch flipped. My relationship with food and my thoughts about food were completely different. The noise is something you don’t even realize is there until it’s not anymore.”
Soliman weighed 250 pounds when he started the drug. In 8 months, he lost 55 pounds. These days, he can forget to eat entirely. On a typical day, when he remembers, he has two protein shakes and a small meal.
Research is beginning to show that these drugs may affect other weight-related health conditions, too. In the SELECT trial, adults with obesity who didn’t have diabetes and received semaglutide were 20% less likely than those on placebo to have a CV event. This benefit arose earlier in the study period than weight loss did. The drugs may improve obstructive sleep apnea, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and diabetic kidney disease.
Like Hughes, Soliman and his wife are on a compounded formulation, too. They get the drug for a few hundred dollars a month rather than over a thousand.
Market disruptor
Given their potential to dramatically suppress chronic disease rates as well as the population’s collective appetite, semaglutide, some predict, may be a major economic disruptor, too. In October of last year, Truist analyst Bill Chappell downgraded his rating for Krispy Kreme from a “buy” to a “hold,” citing the overwhelming use and popularity of appetite-suppressing GLP-1 agonists. That same month, it was reported that the drug’s successes had triggered a sell-off of shares in Dexcom, the maker of continuing glucose monitoring systems, and DaVita, the manufacturer of dialysis machines.
On a microeconomic level, Soliman has certainly seen demand for high-calorie foods plummet in his household. He and his wife, who is also on tirzepatide, buy less at the grocery store, dine out less often, and when they do they order less food.
“We’re splitting an appetizer and maybe an entrée as opposed to two apps and two entrées, and we’re not ordering out as much. It’s curbed all of that,” he said.
But the financial adviser is as struck by the broader market impact of the drugs as he is by the changes he’s seeing in his own waistline and wallet.
“The level of disruption these drugs are creating within industry is fascinating,” he said. “Weight Watchers acquired a telemed company simply so they could start prescribing this stuff to their client base. Medical device companies have seen an extreme dip in their stock prices. The health care industry would save trillions a year if you could actually start eradicating obesity and related ailments.” ■