Glucagon-like peptide-1 receptor agonists, commonly known as GLP-1s, were first developed to treat type-2 diabetes. Since entering the market in 2005, they have exploded in popularity as weight loss medications.

In terms of her health, Rachel Harris has felt like the cards were stacked against her.

A 35-year-old Brockton resident and GLP-1 medication user, Harris had three grandparents with type 2 diabetes; all four had heart conditions. Both of her parents had serious heart and bone issues and she was predisposed to develop high cholesterol.

Half her family is “Southern Black from Louisiana, Mississippi, where everything is deep fried,” while the other half of her family is “Russian Jews, where if you even turn down the concept of being given a meal, it’s an offense.”

Besides being overweight since childhood, Harris experiences chronic pain from endometriosis and four bulged discs in her back, making mobility challenging. For years, she tried tactics to bring her weight down, going to the gym, leading an active lifestyle, and diets such as Weight Watchers. Despite her efforts, her progress plateaued.

“A lot of people think that being overweight [means] you have awful willpower, when a lot of times it’s just your body’s chemistry,” she explained.

Harris was prescribed the GLP-1 Ozempic in April 2024, before transitioning to Wegovy and then Zepbound. The glucagon-like peptide-1 receptor agonists, commonly known as GLP- 1s, were first developed to treat type 2 diabetes. Since entering the market in 2005, they have exploded in popularity as weight loss medications.

The most well-known side effects of GLP-1s are temporary gastrointestinal problems, such as nausea, vomiting and constipation. However, a fraction of users has complained of behavioral changes, such as an inability to feel pleasure, low motivation or a loss of libido. This flattening of emotions is anecdotally called “Ozempic personality.”

As their mass consumption surged in the 2020s, GLP-1s produced a boom in the biotech ecosystem of Massachusetts, with Boston-area startups, pharma giants, hospitals and academic centers keen to study the drugs.

However, insurance providers are introducing a slew of coverage cancellations and restrictions, citing skyrocketing costs. Starting this July, MassHealth is axing standard coverage of GLP-1 drugs prescribed for weight loss, impacting a projected 22,000 low-income and disabled residents.

The Group Insurance Commission, which provides coverage to 460,000 Massachusetts public workers and retirees, voted to do the same. Major local private insurers, such as Blue Cross Blue Shield of Massachusetts, have made similar moves. And due to federal funding cuts to grants for clinical trials and academic research, opportunities are diminishing for the incoming generation of metabolic disease researchers.

GLP-1 drugs alone cannot produce huge weight losses in a vacuum, with physicians citing lifestyle changes like movement and eating adjustments as necessary companions. That said, Harris considers the drugs the “missing piece” she needed to lose 60 pounds.

That change reduced the massive strain on the knee injury that had cut short her cheerleading days, as well as her bad back.

She found herself stretching and moving in ways she hadn’t been able to achieve in a decade. This change is owed not only to the metabolic impact of the drugs but also to their lesser-known neurological effects.

Many patients describe how GLP-1s made them stop experiencing “food noise,” or persistent cravings that occur independently of physical hunger. Recipients often compare the effect of the drugs to wearing noise-cancelling headphones, allowing intrusive thoughts of food to fade away.

Having experienced a turbulent childhood, Harris recounts that food became a way for her to selfsoothe. On top of chronic illnesses sapping her of the time and energy to prepare healthy meals, she found herself eating compulsively as a source of comfort. The reduction of this food noise played a major role in Harris’ weight-loss journey.

This change to patients’ neurochemistry is not permanent. Studies show cravings often come back in full force after a patient stops taking medication, resulting in weight gain. Though GLP-1s quieted the constant “urge in the back of [her] head,” Harris reports that in weeks when she cannot afford her medications, she would start “consistently looking for a snack.” She compared it to smokers craving a cigarette, claiming that it’s similar to “trying to quit an addiction.”

Though GLP-1s are not yet FDA-approved for addiction treatment, there are globally over 15 clinical studies into the subject. Mary Shen, a resident physician at Brigham and Women’s Hospital, studies the relationship between GLP-1s and addiction at the hospital’s Suzuki lab, which examines substance use disorders.

“Anecdotally, physicians were starting to see that their parents were reporting, ‘Oh, I haven’t smoked in a while,’ and ‘Oh, I haven’t had alcohol in a while,” Shen told the Banner.

Because GLP-1 receptors dwell in the brain’s reward centers, the drugs can dampen the dopamine spikes associated with addictive substances, she explained. When an alcoholic gets a drink, for instance, the region of their brain associated with reward “lights up.”

This region, Shen said, shares “a lot of the same circuitry” with other behaviors regarded as compulsive, such as gambling, nail biting, or doomscrolling. Indeed, patients have reported a reduction in all manner of cravings on these medications, beyond food-related urges. Because of this neurological mechanism, researchers are exploring the possibility of using GLP-1s as an “adjunct” to assist in the rehabilitation of addicts.

Most of the research on GLP-1s has focused on combating negative behaviors rather than considering the chance of “dampening the reward for healthy behaviors.” The same reward pathway that allows GLP-1s to blunt unwanted cravings may also theoretically mute the desire to indulge in hobbies, socialization or sex.

Medical experts emphasize that these side effects are rare and large-scale studies show the drugs overall positively impact mental health. Though Shen believes behavioral side effects are “definitely worth counseling patients about,” she affirms that the FDA has extensively reviewed the safety of the drugs.

Harris noted that rather than dampening her personality, the medication allowed her to be “more authentically” herself, because it granted her greater energy, confidence and self-control.

Beyond addiction, some users, including Harris, have reported surprising relief from another chronic condition: endometriosis. The systemic disease affects about 10% of women of reproductive age, whose uterine tissue becomes inflamed and can grow on other organs.

Harris calls it “cancer without the cancer,” referring to how the lesions spread through the body, causing inflammation, scarring and organs sticking together. Lesions can also develop their own blood supply, mimicking the behavior of tumors.

Endometriosis is not a solely gynecological issue. The tissue can grow throughout the body, including the bladder, the lungs and even the brain and eyes. The persistent inflammation can cause extreme pain.

12 years to diagnose, with hospitals frequently dismissing women’s symptoms. The gold standard treatment is excision surgery, but estimates suggest that fewer than 200 endometriosis excision experts exist worldwide. The lack of treatment options, training and research on endometriosis forms a clear modern example of medical misogyny.

In such a grim landscape, GLP-1s may offer a glimmer of hope. Anecdotally, users such as Harris have spoken out about how the medication offered relief for their inflammation. Studies on animals show GLP-1s can quiet pain from nerve signaling pathways, calm the body’s inflammation alarms, soothe the brain, reduce cell damage, enhance cell repair, block scar tissue formation and prevent the immune system from guarding lesions. Data from human subjects show GLP-1 drugs can suppress inflammatory proteins related to endometriosis and cut off the fuel supply of lesions by reducing estrogen production in fat tissue.

Despite this promising preclinical research, there are still no large-scale human clinical trials evaluating GLP-1s as a primary treatment option for endometriosis. Some endo patients, too, find that the gastrointestinal side effects of GLP-1s exacerbate their chronic pain. The drugs require large clinical studies to be considered a legitimate treatment option for the condition.

With the lack of funding afforded to women’s health care, Harris is not expecting to receive GLP-1 coverage for endometriosis any time soon.

“It’s like the light at the end of a tunnel, but...every time you walk forward, it just keeps pulling back,” she said.

In 2023, the American Academy of Pediatrics released new guidelines permitting GLP-1 weight loss medications for adolescents as young as 12. In response to the uptake in GLP-1 usage amongst adolescents, researchers developed the Provider Attitudes on GLP-1 Decision in Adolescents (PRADA) Study to interview primary care and weightloss specialized pediatricians from Boston Children’s Hospital, pediatric private practices and community health centers.

Idia Thurston, a licensed clinical psychologist and professor of health sciences and applied psychology at Northeastern University, is part of the PRADA study team. She emphasized that there is a “real tension” between the urgent need to treat obesity and the unknown long-term consequences of suppressing dopamine during critical windows of brain development.

The demand for prescriptions, she said, has “outpaced” both data and available training. Many pediatricians do not feel equipped to reckon with the challenges of administering these drugs for youth patients — including the potential for eating disorders to develop, drug interactions with other substances such as attention deficit hyperactivity disorder (ADHD) medication and psychological support.

The PRADA study highlights that marginalized groups tend to rely on clinical settings that lack the tools to offer “holistic care.” Thurston observed the greater burden upon community health centers, compared to those in academic medical centers. Unlike the former, the latter could more readily refer patients receiving GLP-1s to behavioral health services. Insurance also played a major role in whether patients could access resources such as mental health care.

Providers who serve Black, brown, low-income and immigrant communities had stronger awareness of the structural issues infringing on their patients’ health but had fewer resources to address them.

“If community health centers by default are having less resources, less training, less opportunity to understand whether GLP-1 medications are even right for their patient population...we should all be concerned, because it is a structural barrier that is not equitable care,” Thurston said.

Black people in America face persistent disparities in both health care and health outcomes. In 2022, they were 35% more likely to die from heart disease, according to the federal department of Health and Human Services. The same year, Black Americans died from diabetes 78% more often than the overall population. They are also more likely to avoid going to the doctor due to fees or being uninsured, and mistrust of the medical profession because of historical exploitation or mistreatment.

Thurston points out that structural factors, such as “being stuck in food deserts,” can be determinants of health, impacting diabetes and obesity rates. Under these circumstances, there is a dire need for research on weight loss, especially within the context of communities of color.

Historically, when Black people are included in research, they are involved as unwilling early test subjects — as in the Tuskegee Syphilis Study, or the stolen cancer cells of Henrietta Lacks. Thurston acknowledges that America has a history of “unfair medical practices on Black bodies.” Where GLP-1s are concerned, she hopes these medications will be properly researched in advance, rather than released to communities of color without prior data.

“We should not be the ones to experiment on the path,” Thurston added.

Harris understands why Black communities would be mistrustful or fearful of going to doctors. She concludes the reality is “doing us a disservice, because so many of us are not getting the treatments that we actually need.”

As insurance companies, including her own, are cutting weight loss coverage for GLP-1s, Harris is growing more frustrated. She previously relied on an amphetamine for weight loss, which she described as “legal speed,” but it interfered with her heart rate. On top of being less effective than GLP-1s, the amphetamine concerned her due to her family history of heart problems. Harris also has ADHD and fears the risk of taking a stimulant on top of her Adderall medication.

Doctors presented her with one other option: gastric bypass surgery, an invasive procedure that would take her out of work. She recalled witnessing a cousin suffer complications, getting hospitalized frequently. Even with coverage, the surgery remains expensive for Harris because, for an insufficiently obese patient, it is considered cosmetic.

Blue Cross Blue Shield’s new restrictions will limit Harris’ ability to afford GLP1s.

“So, you’ll pay for it when I have the diabetes, but you won’t pay for it before,” Harris said. “That’s the point. I’m trying to avoid that. … It’s like it’s penalizing us for wanting to be healthy.”

She voiced concerns about having to pay out of pocket to order medications through shady thirdparty websites, some of which are facing lawsuits. She orders generic Adderall from GoodRx, where it costs about $30, because copay under her insurance would be $120.

“I’m seeing that you’re jacking up the prices and not wanting to cover medications,” she said, alluding to her insurer.

Unreliable access to insurance coverage was one of the focal points of the PRADA study.

“Can people stay on these medications long term? What happens if insurance cuts off after two years?” Thurston said. “We know the data on weight cycling and how it impacts heart health and other cardiovascular outcomes.”

For Brigham and Women’s physician and researcher Shen, the concern, too, remains what happens for patients with addiction facing inconsistent access and rebounds. For example, if an alcoholic resumes drinking after a long period of abstinence, she points out, “their tolerance goes way down. And so, it can pose a much more dangerous issue.”

To support Massachusetts patients like Rachel Harris now living those very scenarios, there is renewed urgency to invest research and resources in GLP-1s.

Physicians worry changes in coverage may undermine patients’ longterm mental and physical health.

If Harris develops diabetes, she will require expensive insulin treatments. If she begins having heart attacks or strokes, she’ll face hospital bills.

“It’s just mind-boggling, and it’s upsetting,” she said of the shortsightedness.