Amber DeBirk tipped the scales at 206 pounds last November and she worried a lot about being around to see her daughters, now 18 and 20, settle well into adulthood. She was turning 50 and wanted time to watch them launch and see who they’d become. But she was worried.

So was Eleanor Barton for much the same reason, though the oldest of her three daughters is just 7.

The two Utah women are among the growing number of Americans who’ve been inspired to try the weight-loss drugs being touted by celebrities, health care providers and others as a real, longed-for breakthrough, even for people who tried for years to lose weight with limited success.

As Americans overall grow heavier — the Centers for Disease Control and Prevention reports as many as 4 in 10 adults are not just overweight, but have obesity and the health risks that come with it — there are a lot of questions about who should or should not take the popular weight-loss injections and about the source of the materials used to make compounded versions of the two types that are arguably most popular, semaglutide or tirzepatide.

Health experts worry about quality control with compounded versions and wonder about the long-term side effects and even whether other proven weight-loss methods like bariatric surgery or better eating habits and exercise will be disrupted by these popular drugs.

Overweight people long starved of hope are lining up as new options appear. But some experts fear people are choosing to be thinner, but not necessarily doing the work to be healthier, too.

DeBirk had gestational diabetes during both of her pregnancies and had been told for years that she was prediabetic. Her family health history included diabetes, heart disease, high cholesterol and kidney issues on both sides — and she’d been taking statin drugs, along with medicine for high blood pressure and to lower blood sugar.

“I was suffering from joint and hip pain due to inflammation, and my triglycerides and cholesterol were dangerously high despite being on medication,” she said.

Barton has thyroid disease and at 5-foot-6 and 208 pounds, she found it hard to be the active mom she wanted to be. Worse, though, was the constant, irritating “food noise.”

Each woman had a prescription for the weight-loss injections making headlines for how well they help adults shed pounds and reduce cardiovascular and other health risks. But their health insurance companies denied coverage, saying their lab tests weren’t bad enough.

But Barton and DeBirk had another option. Prescriptions that contained tirzepatide or semaglutide — the GLP-1 agonist drugs that everyone was raving about and that are the heart of the brand-name weight-loss drugs Zepbound and Wegovy — were in short supply. The FDA was letting compounding pharmacies make similar concoctions to fill the gaps. And the compounded versions were more affordable than the branded drugs for those like DeBirk and Barton for whom insurance wouldn’t pay.

The women describe similar astounding success: In just seven months, DeBirk shed more than 53 pounds. Her triglycerides dropped 200 points, her cholesterol and blood sugar readings are normal. She’s taking half as much statin and her joints don’t hurt. “I just feel really good,” she said.

Barton went from a size 14 to a size 8, the food noise disappeared and she got her energy back. She’s a stay-at-home mom who now easily keeps up with her three young children.

However, what was a battle of the bulge has for many become a battle with the bulge busters. The shortage is over and some who get compounded versions of the weight-loss drugs face uncertainty.

Barton and DeBirk are among patients who fear they won’t be able to afford the medications. Drug manufacturers are already suing some who compound their own versions to force them to stop. And some of the pharmacies are suing back, arguing their compounds are a different formulation, with added vitamins and other things that make them unique. The drug manufacturers don’t own semaglutide or tirzepatide, they argue. They just own their own drug’s recipe.

Dr. Juliana Simonetti, director of obesity medicine and co-director of the comprehensive weight management program at University of Utah Health, believes that people are beginning to better understand that being severely overweight is a disease, not a character flaw, but it’s been a slow process. Stigma and bias are real, even within the medical community, she said.

“I feel like crying because I can’t believe the things people have gone through and how they were mistreated or disregarded based on their weight.” She said it’s not uncommon for people with health complaints to be told to go home and lose weight “without being given any tools to do it.”

Weight-loss drugs are important tools, she said.

Arguably the hottest weight-loss drugs today are those with either semaglutide or tirzepatide as their foundation.

They’re both GLP-1 agonists. GLP-1 stands for glucagon-like peptide-1, which is a natural hormone the body releases to help control blood sugar and appetite. GLP-1 helps the pancreas release insulin, slows down digestion and signals your brain that you’re full.

Both semaglutide and tirzepatide for type 2 diabetes and weight loss are GLP-1 agonists, meaning they mimic the hormone. Ozempic for blood sugar control and Wegovy for weight loss both use different levels of semaglutide, a GLP-1 agonist. Victoza and Saxenda use another GLP-1 agonist, liraglutide.

Tirzepatide — Eli Lilly’s branded versions are sold as Mounjaro for blood sugar and Zepbound for weight loss — works on two hormones. Besides being a GLP-1 agonist, it targets glucose-dependent insulinotropic polypeptide or GIP. GIP and GLP-1 are both “incretins” released by the intestines when you eat, but they don’t work as well when someone has type 2 diabetes, so the addition of the medications help control blood sugar and reduce appetite in cases where the body’s natural versions lag. Because of its dual action, many health care providers favor tirzepatide, but people react differently to the different drugs and for individuals it can be a matter of which works best, has fewer side effects or is more affordable.

Dr. David Gill, senior medical director over Pharmacy Services at Intermountain Health, said the drugs were first developed to treat type 2 diabetes. That patients were also losing weight seemed like a happy side effect. “This is a big deal with type 2 diabetes in particular, because obesity is a factor and is associated with cardiovascular disease and other co-morbidities,” he said.

More recently, semaglutide and tirzepatide have been studied specifically for weight loss. They’re being looked at for other conditions, as well, like liver disease, non-alcoholic fatty liver disease, sleep apnea and potentially kidney conditions. Those are conditions that carrying excess pounds can exacerbate, he said. Some suggest they could help with neurocognitive decline that has a weight and blood sugar component. If weight’s not a factor in the conditions, the drugs likely won’t help.

Though they typically work well for weight loss, Gill said most patients using them for that will not be taking one of the drugs after a year. History suggests that more than half will stop primarily because of the cost or the side effects. Those taking the drugs for type 2 diabetes and blood sugar control are more apt to stay on them.

Gill said the drugs are designed for those who have a body mass index or BMI above 30, indicating obesity. Anyone with a lower BMI number is not eligible unless there’s a diagnosis of a related complication like heart disease.

But some patients who don’t technically qualify find ways around it.

Simonetti notes some GLP-1 medicines have been on the market since 2005. The first GLP-1 weight-loss drug, liraglutide (sold as Saxenda) was approved about 2014, and semaglutide, which came along in 2017, has eclipsed it. The tirzepatide drugs for weight are newer.

There’s plenty of evidence that they are safe, she said. “We have really good data.” The biggest change has been the increasing amount of weight loss patients are getting.

As the number of people with obesity grows, so do the health ramifications, Simonetti said.

“When you have excess weight, it interferes with your joints. So you’re more likely to have knee pain, hip pain, back pain. It can cause sleep apnea, making it harder to breathe,” she said. She noted a “really significant increase in the rates of fatty liver disease that then are leading to liver cirrhosis.” Fatty liver has surpassed alcohol or even hepatitis C for destroying liver function. Additionally, obesity contributes to significant insulin resistance, more diabetes and the related complications.

“If you have a lot of sugar in the blood, it makes it harder for the blood vessels to get the blood flow, and then you have the little vessels being affected in the heart, in the eyes, in the brain, leading to stroke, heart attack and peripheral vascular disease,” she said.

Semaglutide and tirzepatide drugs can restore some of the mechanisms that abnormal weight gain alters, per Simonetti, who sees many reasons for abnormal weight gain, including genetics. In her practice, she has seen patients on weight-loss drugs enjoy better heart and kidney function. Some have had inflammatory disorders like rheumatoid arthritis improve.

“On a weekly basis, I see patients that start crying in my office and say how these medications have been life-altering for them. … They’re walking more. They’re enjoying their families. They are taking trips. Their focus has improved at work without the food noise.”

Gill said that long-term effects are not well-known, but it’s expected that if you’re being successfully treated for obesity, some of the other worries that may go along with it, like heart attack or stroke, or kidney disease, will become less of a risk.

Those improvements save money and pain in the long term.

Simonetti’s not thrown by the notion that someone might need to be on weight-loss medication forever or weight and its many complications could rebound. She thinks of it like high blood pressure or diabetes. You can’t just stop taking those and expect the results to hold, she said.

Gill said the side effects can be hard to handle, including vomiting, nausea, diarrhea and constipation, which is why many patients decide they can’t tolerate them.

Among more than a dozen people on either drug that Deseret News interviewed, reports of side effects varied greatly. Most have some gastrointestinal distress at first. But many of them acclimated quickly. A couple stopped taking the medication because of side effects, though.

“I’ve had patients describe the sensation that food can get stuck or just like, takes a while for food to pass exactly,” Gill said. He also acknowledges rare side effects that need to be considered, too, though they are ”way less common." But gallbladder issues, like gallstones or inflamed gallbladder cholecystitis, pancreatitis, some people get issues where the medicine is injected — pain or infection. “They’re rare, but some people are allergic.”

In rare cases, gallstone issues and pancreatitis occur. There’s a very rare genetic condition that precludes using the medications, as it could increase risk of thyroid cancer. And they’re not for women who are pregnant, breastfeeding or actively trying to become pregnant, Gill said.

Dr. Steven Katz, president of the American Association of Endodontists, warns that people on GLP-1s and other drugs with dry mouth as a side effect — a group that includes some antihistamines, antidepressants, blood pressure medications and certain decongestants— sometimes develop dental problems related to medication.

Anecdotally, endodontists are reporting dry mouth with these drugs, too, though it is not a side effect acknowledged by the manufacturers. Reduced appetite could play a role, he said, since chewing boosts saliva, which helps keep teeth healthy. Additionally, gastric issues can cause dehydration. And reflux “bathes teeth in stomach acid.” Those are all potential side effects of the medications. So folks need to be mindful to protect their teeth from periodontal disease, he said.

He recommends people on weight-loss drugs drink lots of water, avoid sugary drinks and see a dentist twice a year at least. They also need to brush and floss and “be really good about hygiene.”

Katz is among health care professionals who think we may have more to learn about potential side effects. They haven’t been around long enough to know their full story and research keeps offering hints, both good and bad. For instance, he said, he read a study suggesting that older women on semaglutide may, down the road, have lower bone density.

Laura Matjasich, a nurse practitioner in Twin Falls, Idaho, told Deseret News that it’s vital for those using compounded drugs to get the medication from a pharmacy that’s really trustworthy. But she adds that she’s a believer in a compounded form, noting many people she treats cannot tolerate the commercially available doses or need a little lower dose starting out.

She’s one of those people, she said; she has lost 40 pounds in two years on a microdose of tirzepatide. She said she’s benefited greatly. “I’ve watched my insulin resistance decrease, my cholesterol levels decrease, but on a higher dose, I would be so sick.”

Amanda Hanson, a Layton mother of two children, ages 5 and 8, can confirm that the drugs are expensive and the compounded versions are not necessarily consistent. She was daunted by the thought of going to a compounding pharmacy, but wanted to lose weight. She was happy with the first compound and its result, but the price went up when she graduated to a higher dose, so she tried a different, less expensive pharmacy. The medication she received there consistently made her throw up and since she’d already lost 50 pounds, she decided to stop taking the medication altogether.

Gill said that the FDA has raised concerns about compounding, since the regulatory agency doesn’t have oversight and there have been documented contaminations, dosing errors and questions about the countries from which material might be sourced.

He added that some of the compounded medications are mixed with vitamins or other agents to make them different from the patented forms. But those combinations are not the ones that have been studied and for which safety information is available. “At Intermountain Health,” he said, “we prefer to obtain drugs directly from the manufacturer with the specific FDA-approved agent.”

Gill is adamant that it doesn’t matter how great a drug is, weight loss won’t stick around unless lifestyle is modified, too.

“We don’t view obesity as a problem that only needs a drug. We think there could be value with these GLP-1 medications, but that they should be integrated in coordination with lifestyle changes. So we hope to get patients plugged in with a dietician or nutritionist or in an exercise program. Some people have behavioral health needs associated with obesity, so that’s important. And some patients would be better suited for something like bariatric surgery.”

Simonetti agrees that lifestyle changes must be embraced, like nutritious whole foods and fewer carbs and processed foods. Rich, fatty foods are apt to trigger gastric side effects, too. Diet and exercise are foundational to weight loss, but she said the medications make it easier. She’s also adamant that people on the medications do strength training, because as they lose weight, they lose muscle mass. And aging itself reduces muscle mass. So resistance training matters.

“If we are able to keep our muscle mass, then we are able to keep our mobility and have less risk of falling and other complications,” she said.

Once she’d gotten a prescription and started losing weight, Hanson described her efforts to change her lifestyle as “die hard.” She quit drinking soda, she kept track of how much protein she was eating and she drank a lot of water. “I was eating really, really well. I was staying away from carbs because I was investing all this money and decided I just gotta do this,” she said, although she adds she didn’t exercise as consistently as she could have.

When she stopped taking the medication, Hanson’s weight rebounded and she regained all but 15 pounds, though her better eating habits have remained with her. She’s sad that she couldn’t afford the rising costs or tolerate the side effects. On the drugs and carrying less weight, she loved how she felt. She had more energy. “I obviously felt better about myself. So I would have stayed on it if I didn’t have those side effects and if I could have afforded it.”

Mary J. Charlot, a family nurse practitioner in Lithia Springs, Georgia, whose specialty includes weight management, said that any provider prescribing the medications should also be educating their patients on the importance of optimal wellness: eating healthy meals, physical activity, processing stressful emotions, maintaining proper work-life balance and finding an inner calm and peace. “Obesity is a multi-dimensional issue, so other tools such as physical movement, nutritional coaching, and surgery will always be needed.”

Dr. Jennifer Brown treats patients in Lewisburg, West Virginia, and reminds them that the good things you do that bolster well-being and health really matter.

“Healthy eating and being physically active positively affect the body outside of weight loss. People on semaglutide can still eat junk food and lose weight, but they may develop vitamin and mineral deficiencies or even malnutrition,” she said. “Exercise is also vitally important for those on semaglutide; it helps to preserve muscle mass while losing weight. Anyone with an eating disorder who is on semaglutide and not in an intensive behavioral program can develop even more dysfunctional food behaviors.”

Matjasich said there are people for whom she would never prescribe semaglutide or tirzepatide. If someone’s pregnant or has a family history of medullary thyroid cancer, it’s a hard no. Same for someone with a history of any type of eating disorder. But the drugs can be a blessing for others, she said, including people with polycystic ovary syndrome who have a genetic predisposition to weight gain that’s hard to conquer.

She has seen patients slowly come off the medications successfully and keep their weight off. They’re the folks who have done the hard work of changing their lifestyles.

Cost is no joke for some of the people who most need medications to help stabilize their weight. Even with insurance, out-of-pocket costs can be in the hundreds of dollars a month. Simonetti said a lot of her patients can’t afford the medicines. But she believes that access has improved and costs are coming down. Drug companies are offering a direct pharmacy option at a bit lower cost. They’re working with patients and insurance companies to create more access.

But one barrier she noted is the idea put forth by many insurance companies that being overweight — and the steps to reduce that weight — are cosmetic. She refutes that vehemently. “It truly is not,” she said, while acknowledging that some patients want the weight-loss drugs to lose a few pounds or just look better.

For those for whom the drugs are intended — those who are clearly overweight or suffering health effects — the cost of care for the related health problems add up, too, she said. The quality of life for patients who can get off medications like insulin or statins or other drugs, who feel healthy enough to exercise sometimes for the first time in ages, who feel better about themselves— for them, it’s hard to calculate a price tag.

“This is a revolutionary time and I feel fortunate to be practicing in the day and age when we have a lot more access to help for patients,” Simonetti said.

None of the health care experts interviewed for this story believe that other weight-loss efforts will go away. Some people are better suited for bariatric surgery than for medication.

“We want to make sure people are aware of all the options available,” Simonetti said. “We’re moving toward this precision medicine; what works for someone might not work for the next person. But I can’t say enough how revolutionary the drugs are in the sense that they really have been changing people’s lives.”

Charlot predicts the impact on the health and wellness industry as a whole will be neutral. “The health and wellness industry is very vast with everything from protein shakes, fitness trainers, detoxes, the next fad diet, yoga, medications, surgeries, etc. People will always shift and move depending on where their personal goals are,” she said.

“For that reason, I think it’s so important for us not to judge others for the choices they make while on this journey. I will also say that the common goal for all people that are on some type of health and wellness journey is that they are in search of self-love and self-acceptance, and that journey can look different for different people.”

Barton said she worked hard to love her body and be confident despite the number on the scale. It’s a message she hopes her daughters will see.

Dr. Wilson Beltre, a board-certified bariatric surgeon in Orlando, Florida, said that since semaglutide was introduced, most bariatric surgeons in the U.S experienced a drop in volume of 50% or more, but like weight for some patients, it’s rebounding. “Interestingly, volume is picking up again because people are realizing that semaglutide is not for everyone due to side effects, or some regain the weight after stopping the injections.”

Meanwhile, health care providers are pondering who should and shouldn’t use the medications and why. And it’s a field where change is becoming constant. Dozens and dozens of new potential medications are somewhere in the research and development pipeline.