The Agonists and the Ecstasy

The popularity of GLP-1 agonists to treat obesity has been skyrocketing in recent months, leading to both shortages and price increases. However, as more patients make their voices heard and doctors begin to prescribe them, obesity could become easier to treat or even cure.  

Thanksgiving is a time for family, fellowship, and food. But for many struggling with obesity, the holiday can bring on another association: fear. For some, the obsession over how much to eat or not eat can take over, and what’s supposed to be a joyous and celebratory occasion is overshadowed by anxiety and shame.

Fatima Cody Stanford, MD, MPH, MPA, MBA, associate professor of medicine and pediatrics at Harvard Medical School and an obesity medicine physician at Massachusetts General Hospital, treats a 64-year-old woman with obesity whose Thanksgiving experiences had been like that all her life, her mind on that day spent consumed with how much she could eat and what activities she could do, until just recently. Stanford prescribed the woman a glucagon-like peptide 1 (GLP-1) agonist, and the woman was happy to report back that this past Thanksgiving was the first time she didn’t fear Thanksgiving dinner.

“She said, ‘This is the first Thanksgiving I’ve been to where I wasn’t obsessed about, okay I can’t eat this much, or I can’t do this. I knew my body would do what it was supposed to do. I could still enjoy dinner, and then move on the next day,’” Stanford says. “And she had so much joy emanating from her to tell that story.”

GLP-1 agonists have been around for a while. Still, they’ve been in the spotlight again of late, especially with recent headlines about Ozempic and Wegovy (semaglutide), as gossip swirls about what celebrities have been taking semaglutide to slim down to fit into dresses or look thinner in photoshoots. And GLP-1 agonists have shown to be effective: liraglutide, with its daily injections, could result in about 6% total body weight loss. But semaglutide is a weekly injection, and Stanford says people are seeing total body weight loss of 15% to 16%. “It’s kind of like a no-brainer,” she says. “Which one would you want?”

“Obesity is a complex pathophysiologic disease and under both homeostatic and hedonic control,” says Amy E. Rothberg, MD, a clinical professor at the University of Michigan, specializing in treating overweight and obesity. “What’s novel about current medications is that they address more than one target or pathway in both these systems, working well to reduce hunger, enhance satiety, and facilitate lower intake leading to weight reduction. They also have excellent safety profile and lead to benefits independent of weight loss.”

“For patients with diabetes, there have been studies showing that medical providers are less likely to prescribe certain medications to commercially insured patients who are Black, than they are to those who are white. These practices may be due to medical providers having biases about which patients will be able to afford certain medications, or about the effectiveness of medications in different patient groups.”

Rocio Pereira, MD, chief of Endocrinology, Denver Health; associate professor of medicine, University of Colorado, Aurora, Colo.

Rocio Pereira, MD, chief of Endocrinology at the safety-net hospital system Denver Health and an associate professor of medicine at the University of Colorado, says that many of her patients report that semaglutide helps them eat less and that it has become easier for them to eat healthy foods and avoid junk food since starting on the medication. “I had anticipated that many patients would not want to start an injectable medication, but this has not been a barrier for most of my patients, and the availability of a medication that can be injected once weekly has made it possible for more patients to agree to try,” she says.

And as the buzz on these medications, especially semaglutide, grows louder, people are flocking to doctors or the black market to get their hands on them, even people who don’t have obesity or diabetes. But with that influx comes headaches for the patients seeking the drugs, and the physicians who prescribe them.

Pereira says that medication shortages impacted her patients, who had to switch to less effective drugs, which is especially concerning for patients with diabetes who need the medications to keep their blood glucose in a safe range. “It is also an issue affecting patients who had started losing weight but then are not able to continue taking the medication and start to gain weight again,” she says.

Compounding the problem is the fact that insurance companies are reluctant to cover these anti-obesity medications, since they’re considered by many to be “vanity drugs,” even though overwhelming evidence suggests obesity is linked directly to multiple comorbidities.

“Obesity impacts health,” Rothberg says. “As we know, there are more than 230 conditions associated with obesity. Treating these conditions poses a high economic burden. It is entirely short-sighted not to cover these medications which are likely to facilitate remission of other conditions, saving the insurance from downstream costs. These changes occur quickly so it’s not a long-time horizon to realize these benefits (from a sheer cost perspective).”

Obesity: A Dynamic Endocrine Issue

In June 2013, the American Medical Association acknowledged obesity as a disease, writing in its resolution, “The suggestion that obesity is not a disease but rather a consequence of a chosen lifestyle exemplified by overeating and/or inactivity is equivalent to suggesting that lung cancer is not a disease because it was brought about by individual choice to smoke cigarettes.”

Ten years later, and there’s much more work to do. Obesity is considered as a “cosmetic disease” or a lack of willpower. Here’s an example of just how long the road ahead is: Stanford tells Endocrine News that she was recently interviewed by a reporter from a large, national publication, who asked her, “You’re talking about medications? Don’t you need to tell them to exercise or something?”

“I said, ‘That’s a very biased response,’” Stanford says. “I said, ‘The patient I saw yesterday has completed 30 triathlons. How many have you completed?’ The assumption, if you saw this person come in and you didn’t know anything, you would presume, ‘Oh, they’re not active. Oh, they’re not doing this.’ But if you take the time to listen to what they’re telling you, they’re telling you what their life has been.”

Stanford says that the medical community has not treated obesity as a disease until now. She points out that less than 3% of the population has been getting therapy beyond lifestyle modification. “We would lose our medical license if a patient came in with diabetes and we said, ‘I know you’re here admitted in the hospital and you have diabetes ketoacidosis, and I think you should eat less sugar. If you eat less sugar, can you do that? Okay, all right, so I’m going to give you some water, and you really should exercise and eat less sugar, and everything will be okay.”

“Look at the scientific evidence. Look at the sheer number of people affected. This is not an isolated problem. People are NOT choosing to have obesity. We must not consider fat to be anything other than what it is: a dynamic endocrine tissue that has interplay with other organs/tissues and poses risk to health.”

Amy E. Rothberg, MD, clinical professor, University of Michigan, Ann Arbor, Mich.

Rothberg says there’s an undue stigma associated with obesity that permeates all aspects of our society and healthcare systems, much like the stigma surrounding patients with HIV and AIDs in the 1980s. “Many blamed the victim,” she says. “Because of the stigma, individuals living with obesity are reluctant to ask for help and do not access resources that could help them. They, themselves, may feel that their obesity is a matter of personal failure and are unaware that it is a condition that has a biological basis and for which there are therapies.”

And the reason for that reluctance is causing actual harm. Only about 3.6% of people with obesity seek medical care from a doctor, even though about 90% of people with obesity want to lose weight. “Traditionally, we’ve been the worst place to go because we were going to say exactly what I just said: ‘All right, but are you sure you’re really eating well? I don’t know. Tell me what you really did,’” Stanford says. “If that were what you got from your doctor, would you want to bring it up? I wouldn’t.”

“It’s so pervasive in the medical community that we’re not willing to listen to the most important person in the room,” she continues, “and that is not us, however many degrees we have. It is the patient.”

“Look at the scientific evidence,” Rothberg says. “Look at the sheer number of people affected. This is not an isolated problem. People are NOT choosing to have obesity. We must not consider fat to be anything other than what it is: a dynamic endocrine tissue that has interplay with other organs/tissues and poses risk to health.”

Raising the Patient’s Voice

No one is arguing diet and exercise shouldn’t be included in regimens for people with obesity. But these current anti-obesity medications may start turning things around, as more physicians are willing to prescribe them, and more patients are eager to ask for them. And for patients with obesity, these medications can be lifesaving.

Rothberg has a patient who was struggling with weight and poor glycemic control, who was taking around 100 units of insulin, oral anti-diabetic medications, and anti-hypertensive medications. “We were MANAGING her disease,” Rothberg says. “She was perpetually discouraged by her inability to make meaningful lifestyle changes that translated to changes in weight and therefore, any medication reduction or improvement in outcomes. Weight affected almost every aspect of her health and her quality of life. She is now taking a GLP1RA that has made transformative difference in her weight (she lost 20 pounds over two months) and metabolic control. She was able to reduce her insulin to 10 units and may likely discontinue it as she loses more weight and discontinued her oral anti-diabetic medications in the same interval. She is ecstatic and her vitality/energy/mood and outlook on life have all improved.”

Stanford sees similar results in her clinic, with patients able to reduce insulin or come off anti-hypertensive drugs altogether. She’s able to delete diagnoses off their charts, often showing patients just how much they improved over a year, letting them view lab results side by side, where they can see improvements in liver function, cholesterol values, and blood sugar. “This is not just about looking cute in a bikini somewhere,” she says. “Unfortunately, there are people that are using it in that way, but let’s look at the bigger issue, which is changing lives, changing health status, changing health risk, decreasing the risk of heart attack and stroke, admission for heart failure, kidney numbers. We can keep going on and on. This is what all the trials are showing us.”

But barriers to accessing these medications remain. Pereira points to the disparities that contaminate the issue, and the irony that those who need these medications the most won’t be able to take them. Individuals with lower socioeconomic status and those from under-served and minority communities are more likely to have obesity and obesity-related complications than those from higher socioeconomic status or those from privileged and/or majority groups. “Inequities in access is also an issue,” she says. “For patients with diabetes, there have been studies showing that medical providers are less likely to prescribe certain medications to commercially insured patients who are Black, than they are to those who are white. These practices may be due to medical providers having biases about which patients will be able to afford certain medications, or about the effectiveness of medications in different patient groups.”

And again, not all insurance companies will cover them, and even if they do, co-pays and out-of-pocket costs can be prohibitive. “There are also prescribing limits,” Rothberg says. “Further, there were shortages of these medications that created access problems including no new starts and for those who had been on medications, not being able to get their medications in a timely manner. Many were out of their medications for weeks to months, which compromised their care.”

But Stanford says patient voice is again key here. At one point, in Massachusetts, only two private insurance companies covered anti-obesity medications, until patients started leaving their respective insurers and shifting to the two that paid for the medications they wanted. Now all private insurers in Massachusetts cover these medications. “Patient voice is much more important than any of us that are clinicians or experts in the field,” she says. “We may think very highly of ourselves, but the patient voice is way more important in terms of what happens in reality.”

“We have to be willing to listen to the patient and treat them with dignity, respect, and let their voice be heard and elevated, and put ourselves aside. We’re not the most important person in the room. They are. If a patient comes in who weighs 500 pounds, and we never say anything other than, ‘Oh yeah, just eat less, exercise more; it’s totally fine.’ It’s not fine, and so we have to be willing to recognize that we’ve been at fault, and we can do better if we’re only willing to.”

Fatima Cody Stanford, MD, MPH, MPA, associate professor of medicine and pediatrics, Harvard Medical School; obesity medicine physician, Massachusetts General Hospital, Boston, Mass.

Both Rothberg and Stanford agree that the first step toward treating patients struggling with obesity is to listen to their stories, to hear what they’re telling you, to treat them with empathy. “They are often your family member, your neighbor, your work colleague or even your healthcare provider,” Rothberg says. “For those who do interact with patients, remember to be sensitive to your patients with obesity as they have many challenges beyond just those for which they may be consulting you. They are faced with all sorts of discrimination. Your thoughtful communication can go a long way in forging a connection and helping them lose weight.”

Obesity is a chronic, relapsing, remitting, multifactorial disease, for which different therapies may be effective for other patients. “We have to be willing to listen to the patient and treat them with dignity, and respect, and let their voice be heard and elevated, and put ourselves aside,” Stanford says. “We’re not the most important person in the room. They are. If a patient comes in who weighs 500 pounds, and we never say anything other than, ‘Oh yeah, just eat less, exercise more; it’s totally fine.’ It’s not fine, so we have to be willing to recognize that we’ve been at fault, and we can do better if we’re only willing to.”

Bagley is the senior editor of Endocrine News. In the March issue, he wrote about the remarkable life and career of Nobel Laureate Rosalyn Yalow, PhD, the first woman president of the Endocrine Society.