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Learning from Those with Lived Experiences

Lived experiences personalize the benefits and risks involved with the use of glucagon-like peptide 1 receptor (GLP-1R) agonists, said Kimberlei Richardson, an associate professor in the Department of Pharmacology at the Howard University College of Medicine. Two individuals with direct experience with GLP-1R agonists shared their perspectives. They spoke

about the stigma that people with obesity or neurological disorders often face, their struggles to find effective treatments, and their experiences with the new GLP-1R agonists.

AN EXPERIENCE WITH BINGE EATING DISORDER AND OBESITY

Patricia Nece, a member of the National Academies Roundtable on Obesity Solutions¹ and the immediate past chair of the Obesity Action Coalition, spoke about her experiences with binge eating disorder and obesity. “I’ve had obesity since childhood,” she said. “I don’t remember a time when I wasn’t one of the biggest people in the room. That, of course, exposed me to bullying, bias, stigma, and discrimination.” And the effects of that stigma and bias are incredibly harmful.

She was always a very active kid, Nece said. She was on swim teams—including a synchronized swim team in college—rode a 10-speed bicycle for transportation and did gymnastics. “I was always very active, yet my weight was always high,” she said. And although she found success in other areas of her life, including her professional and family life, she could never control her weight despite trying multiple diets. “I would lose some weight, and it would come back. I’d lose weight again on a different diet, and it would come back, usually bringing a few friendly extra pounds with it.” As a result, she blamed herself for not being able to maintain the weight loss, she said, because that is what she consistently heard from medical professionals, the media, family, friends, and society in general.

It was only when she was in her 50s and started working with an obesity medicine specialist that she realized that obesity is a disease involving complex factors. At that point she had lost 120 pounds by pairing medical treatment with psychological treatment aimed at helping her cope with the weight bias that she had internalized and to reduce the stigma she felt. She also discovered that she had binge eating disorder. The binges had always been part of her life, she said, but she “didn’t really see them as different or something that maybe I could seek treatment for.”

Still, after Nece had lost the 120 pounds, she had difficulty maintaining the lower weight, and she started to regain some of it. That led her to start taking medication. She began with lorcaserin, marketed as Belviq, which helped her maintain the weight loss, though she did not lose much more. What it did help with, Nece said, was what she called the “food noise”² in her brain, the way she talked to herself about food. However, the drug’s

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¹ For more information on the Roundtable on Obesity Solutions, see https://www.nationalacademies.org/our-work/roundtable-on-obesity-solutions (accessed November 11, 2024).

² Food noise refers to the intrusive thoughts about eating and food that can make it difficult for some people trying to lose weight to resist eating food that is not part of their diet.

manufacturer pulled it from the market in February 2020 at the request of the FDA because an increased risk of cancer had been observed in people taking it.

During the COVID-19 pandemic, Nece gained 50 pounds, which led her to decide, in consultation with her obesity medicine specialist, to try a GLP-1R agonist. She started with semaglutide, taking half of the normal starting dose for the treatment of diabetes. Unfortunately, it gave her severe intestinal and digestive problems, and her specialist told her that, judging from the experiences of his other patients, she would probably not adjust to those side effects. “The sad part was, I was pretty sure it was working,” Nece said. “I can tell you exactly the place and time when my appetite returned.”

It took her about 2 years before she was ready to try again, at which point she went with tirzepatide, which is a dual agonist for both GLP-1R and the glucose-dependent insulinotropic polypeptide (GIP) receptor. She was somewhat fatigued at the beginning and had a few gastrointestinal issues, but overall, Nece experienced few side effects, and she felt it was a successful drug for her. It helped with her binge eating disorder, in large part, she said, because it cut down on her normal food noise. Even when she drove past fast-food restaurants on her way to and from work, she no longer found herself thinking about food. The combination of psychological therapy and tirzepatide provided her with enough support that she could control her symptoms. And since Nece has started taking tirzepatide, she has lost about 20 percent of what she weighed at the time she began.

Despite the success that she and others have had with GLP-1R agonists, Nece said, a number of challenges remain, related to the effective prescribing and use of the drugs. One of the key challenges, she said, is training the people who prescribe them. In her experience, she said, doctors treating patients with obesity often write a prescription without providing any support for the patient or even offering any detailed instructions. She herself responded to tirzepatide by hardly eating at all. Fortunately, she continued, she had the resource of a nutritionist, who worked with her to develop a plan that combined her tirzepatide with an appropriate diet. However, most patients do not have that resource, she said, so training more providers in this area will be critical.

A second challenge, Nece said, is the silos that have been built between physical health and mental health. When discussing obesity with a patient, doctors rarely touch on psychological health, she said, but they should. She said this is particularly important for patients being put on GLP-1R agonists, since the drugs can lead to dramatic behavioral changes. In her case, she said, her entire approach to eating changed almost overnight from what she had known her whole life.

A SUCCESS STORY OF USING A GLP-1R AGONIST TO LOSE WEIGHT

Karen Glanz, George A. Weiss University Professor at the University of Pennsylvania Perelman School of Medicine and School of Nursing, spoke about her experiences using a GLP-1R agonist to lose weight, lower her cholesterol, and improve her liver function. She approached the topic as someone who has also conducted research in the field of obesity, nutrition, and activity for several decades (Glanz et al., 2005, 2006, 2021, 2023; Sallis and Glanz, 2009).

During that time and earlier years, she had her own struggles with weight, losing a substantial amount of weight, regaining it, losing it, and then regaining it. “This is a story that I think many people who are patients with these drugs have probably been through,” she said, “and it’s the biology as well as the behavior.”

She had always followed a healthy eating lifestyle, and her interest in physical activity and her passion for an active lifestyle grew when she started triathlons. She loved the idea of physical activity as the way to a healthier body and mind, she continued, but she felt somewhat embarrassed to wear swimsuits and sports outfits that exposed more of her body. Despite this, Glanz said, she “continued [physical activity] with all the ups and downs of the weight.”

Then, in 2023, Glanz’s primary internist recommended that she should go on a statin, a cholesterol-lowering drug, for her high cholesterol. Glanz, frustrated with her weight struggles, asked about being prescribed a GLP-1 drug, specifically Wegovy, which her doctor did. But after getting the prescription and insurance authorization, the drug was not available. After a number of months of waiting, she found out from a colleague that if she switched from a commercial pharmacy to a university-based specialty pharmacy, she could get medication in a higher dose, so her doctor agreed to start her on Wegovy at 0.5 milligrams.

In nearly 11 months, she lost 46 pounds (Figure 3-1). Furthermore, her low-density lipoprotein (LDL) decreased significantly as she was taking both a statin and Wegovy, and her liver function tests returned to normal. “For me, this has been a miracle drug,” she said.

DISCUSSION

Fatigue as a Side Effect of GLP-1R Agonists

Ellen Mowry, a workshop participant from Johns Hopkins University, asked Nece about the fatigue she reported experiencing when on GLP-1R

agonists. Nece said that on the day after she took the first dose of tirzepatide, she did not wake up until 1 p.m., when normally she had been waking up at 9:00 a.m., and she only woke up then because her doorbell rang. She did not feel fatigued while awake, she said, but she slept much more than usual. Now, after about a year of taking tirzepatide, the effect has gotten much better.

Jon Davis, a principal scientist at Novo Nordisk, added that researchers do not really understand the mechanism behind the sleepiness or fatigue caused by these drugs, but it would make sense that a tremendous reduction in appetite and caloric intake over a prolonged period of time could lead to fatigue. And Hayes commented that the typical satiety response includes sleep and rest, so the additional sleep that Nece experienced might be related to a satiating response. Finally, Patricia Sue Grigson, professor and chair of the Department of Neural and Behavioral Sciences at the Penn State College of Medicine, said that some of her rodent studies found that the rats had an increase in non-REM sleep following treatment with liraglutide (Fang et al., 2023).

Decreasing the Stigma Associated with Using GLP-1R Agonists

In response to a question about ways to decrease the stigma surrounding usage of the GLP-1R agonist, Nece said that weight bias, stigma, and discrimination are ubiquitous in society and that every individual can help make a difference. “I think the way to attack stigma with these medications is for everybody to start understanding what weight stigma is and speaking out about it,” she said. She urged the members of the audience to start by examining their own internal biases. “The next time you’re seeing somebody my size walking down the street, start noticing what are your automatic assumptions about that person. If you saw me, would you think I was even interested in weight management? You might not, but yet here I am.” The next step is for people to speak out whenever they witness weight stigma, Nece said. “I think until we reduce weight stigma in society, we’re going to have this problem.”