When her primary care doctor mentioned a new kind of medication for weight loss, Taegan Byers was cautiously optimistic.

She’d been struggling with weight gain ever since getting diagnosed with polycystic ovary syndrome as a teenager. She then developed prediabetes, high blood pressure and cholesterol, asthma and depression.

Byers, now 22, had tried all kinds of different methods to lose weight, through exercise and nutrition only, or drugs that suppressed appetite or insulin resistance. Nothing made much of a difference.

“I would maybe lose a few pounds and it just was so discouraging,” Byers said. “Like, what’s the point of continuing to go to the gym, what’s the point of continuing to eat healthy, and nothing’s happening, and I still feel like crap.”

But her doctor said this new option was different. So she started injecting herself once a day with liraglutide, a type of glucagon-like peptide-1 receptor (GLP-1) medication.

“And immediately, there was just a complete shift in my energy, and the response was great. I lost 20 pounds in two weeks,” Byers said. “I was just eating healthier, I was exercising, it was like a switch just flipped.”

That was nearly four years ago. Byers eventually switched to Wegovy, a GLP-1 medication recommended for obesity and weight loss, and has since lost 100 pounds. Most of her chronic health conditions have resolved, and her mental health has improved drastically.

“I can confidently say it’s changed my life,” she said. “I know it’s not a one-size-fits-all, but it definitely worked for me.”

Now, Byers said she fears what her treatment plan and future will look like after her health insurer, Independence Blue Cross (IBX), announced it would restrict coverage for GLP-1 and other weight loss medications beginning Jan. 1, citing the high costs of the drugs.

Uncertain future for GLP-1 users as insurance limit reimbursements

Byers lives in Michigan, but gets health insurance through an employer based in Pennsylvania.

Patients can still get coverage if they have a diagnosis of Type 2 diabetes, cardiovascular disease or sleep apnea, but not if they have obesity only or for weight loss generally. They may face paying the full pharmaceutical sticker price of these drugs out of pocket, which could be as high as $1,350 a month.

“We know how much we pay into premiums and our deductibles, and at the end of the day, this is just a really selfish decision on their part because people are going to suffer from it,” Byers said.

IBX joined other major insurers like Kaiser Permanente, Blue Cross Blue Shield of Michigan, Mass Health, North Carolina’s State Health Plan and others in restricting or dropping coverage for GLP-1 medications.

Some insurers in Pennsylvania and elsewhere never covered the drugs for obesity or weight loss only.

In a Nov. 1 memo to plan members, IBX officials stated that coverage for these high-cost drugs could drive up premiums for everyone, not just people taking the medications.

“These exorbitant costs have made it extremely challenging to be able to continue to provide drug coverage to everyone who wants these drugs but does not have an FDA-approved medical condition or indication for these drugs,” the memo stated.

Insurers also point to inconsistent use of the medications. A report from the Blue Cross Blue Shield Association’s data analytics arm showed that less than half of people who got GLP-1 prescriptions stayed on the medications beyond 12 weeks.

“Most people haven’t stuck with GLP-1s long enough to see a benefit,” said Dr. Razia Hashmi, the association’s vice president of clinical affairs. “This illustrates that there is much more to learn.”

Hashmi and insurance experts estimate that at the current list prices, it could eventually cost “over $1 trillion per year” to make GLP-1 medications available to all obese Americans.

“When families and employers make a significant investment, we want the result to improve health. Otherwise, we are contributing to the country’s health care affordability crisis,” Hashmi said. “Unfortunately, weight loss is not as simple as filling a prescription. Patients have the greatest chances of success when these medications are paired with lifestyle changes and collaboration with their health care provider.”

But Byers said limiting coverage for everyone hurts people like her, who are consistent in taking the medications and have made significant lifestyle changes. She argues that health insurers will still incur costs in the long run if people can’t use GLP-1 medications to prevent more serious health conditions that can develop from obesity.

“Whether it’s paying for a heart surgery for someone who has a clogged artery or a bariatric surgery for someone who is obese … it’s going to cost the insurance company something,” she said. “It’s up to them to decide how they want to pay for that.”

It’s a stressful situation, Byers said. The good news is that her IBX employer-sponsored coverage will continue to cover her medications through July, when the current plan ends. However, after that, she confirmed with the insurance company that coverage for Wegovy would mainly apply to certain conditions, but not for weight loss or obesity only.

“I think it sends a really terrible message to the public, which just kind of reinstates the stigma around obesity, saying that this is not a disease, this is a choice,” she said. “When we know through decades of research and [from] obesity specialists saying that this is a chronic disease and it does need to be treated.”

Patients scramble for new solutions

As a small business owner in Philadelphia, Rich Venezia buys his health insurance directly from IBX. He started taking Zepbound, a brand of the GLP-1 medication tirzepatide, in late September after hearing success stories among family and friends.

With some insurance coverage and a discount coupon from the pharmaceutical manufacturer, Venezia paid about $350 for a month’s supply of injections after meeting his deductible.

“Which was still a lot of money, but I thought, well, compared to the $1,100 or $1,300 [list] price, that was manageable,” he said.

But Venezia said he didn’t get a notice from IBX about changes to coverage for GLP-1 drugs until late December, which left him with little time to request additional refills before Jan. 1.

“I could have gotten myself a three-month supply and been able to at least have the ability to figure out what I was going to do,” he said, “but not having any time and having to scramble for no reason … that inability to make those decisions for myself when I am paying my monthly bills to this agency as their respected customer, it felt like an affront.”

In a statement, IBX said the company began notifying employer groups about the coverage change as early as August. They sent direct notices to individual plan members on Nov. 1 if they had been prescribed weight loss drugs before Sept. 4.

For people like Venezia, who started taking medication in late September or later, a second wave of notices was sent on Dec. 16.

After struggling with obesity and previous weight loss attempts over the years, Venezia said Zepbound has supported his efforts in keeping to a daily schedule of gym workouts and a high-nutritional meal plan.

The drug, which helps control appetite by slowing down digestion and making people feel fuller faster, also helped Venezia to identify and recognize what was triggering his past stress and binge eating.

“Once you have more knowledge about them and how your body is affected by stress eating and how much food you actually really need to feel satisfied, it certainly could make a long-term difference,” he said.

Without insurance coverage, Venezia said he is looking at paying about $650 a month. He said he can afford that in the short term, but it’s not something he can or wants to do indefinitely.

“I’m going to kind of reassess every time it’s due to order another box and see like, okay, do I want to spend this?” he said.

From a business perspective, Venezia said he doesn’t begrudge IBX for making this decision or the pharmaceutical companies from making money. What makes this situation upsetting, he said, is the sudden loss of his coverage, the limited timeline of communication, and the lack of affordable treatment options.

“I’m one very small fish in their very large pond of how they make money, right? But even still, when it comes to health care, it all feels really personal, right?” Venezia said. “It’s about how you feel and how you get through the world, and if you don’t have good health and good health care, it affects every other aspect of your life.”

Staphylococcus aureus is a leading cause of antibiotic resistance-associated infections and deaths. It is also the most prevalent bacterial infection among individuals with diabetes mellitus (DM), a chronic condition that affects blood sugar control and reduces the body’s ability to fight infections.

A study by scientists at the University of North Carolina School of Medicine found that in diabetic mice with an S. aureus skin and soft tissue infection (SSTI), the bacterium evolves antibiotic resistance rapidly, whereas resistance didn’t occur in nondiabetic mice over the course of infection. Results from the study, headed by microbiologists Brian Conlon, PhD, and Lance Thurlow, PhD, showed how the diabetic microbial environment produces resistant mutations. The findings also demonstrated that controlling the blood sugar of diabetic mice with insulin resulted in significantly decreased incidence of antibiotic-resistant S. aureus. The study results point to potential approaches to combatting antibiotic resistance in individuals with diabetes.

“We found that antibiotic resistance emerges much more rapidly in diabetic models than in nondiabetic models of disease,” said Conlon, associate professor at the department of microbiology and immunology. “This interplay between bacteria and diabetes could be a major driver of the rapid evolution and spread of antibiotic resistance that we are seeing.”

Conlon, Thurlow, and colleagues reported on their study in Science Advances. In their paper, titled “Diabetes potentiates the emergence and expansion of antibiotic resistance,” the team noted, “In total, this work establishes a direct relationship between diabetes and the emergence and proliferation of AMR … The data presented here may inform the development of treatment strategies and highlight the crucial need for the development and implementation of more effective antibacterial compounds to improve infection outcomes in individuals with diabetes.”

Antibiotics are powerful, fast-acting medications designed to eradicate bacterial infections. However, in recent years, their dependability has waned as bacterial resistance spreads. People with DM are more susceptible to bacterial infection, leading to a high frequency of severe and chronic infections in individuals with DM, the authors noted. “Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment … Antimicrobial resistance (AMR) further complicates the treatment of infection in individuals with DM.”

Diabetes affects the body’s ability to control glucose, often causing excess glucose to build up in the bloodstream. Staph feeds off these high sugar levels, allowing it to reproduce more rapidly. “S. aureus uses glucose as a preferential carbon source and becomes hypervirulent in a diabetic SSTI infection,” the scientists further stated. The bacterium can also grow without consequence, as diabetes also impairs the immune system’s ability to destroy cells and control infection. “The increased susceptibility to infection in individuals with diabetes is due to a combination of factors including immunosuppression, hyperglycemia, and lack of vascularization in the extremities,” the scientists further explained. SSTIs in diabetic individuals are frequently severe and may necessitate amputation, especially in the extremities such as toes and feet.

As the numbers of bacteria increase in a diabetic infection, so does the likelihood of resistance. Random mutations appear and some build up resistance to external stressors, like antibiotics. Once a resistant mutant is present in a diabetic infection, it rapidly takes over the population, using the excess glucose to drive its rapid growth.

“Staphylococcus aureus is uniquely suited to take advantage of this diabetic environment,” said Thurlow, assistant professor of microbiology and immunology, with joint appointments in the UNC School of Medicine and the Adams School of Dentistry. “Once that resistant mutation happens, you have excess glucose and you don’t have the immune system to clear the mutant and it takes over the entire bacterial population in a matter of days.”

Conlon, an expert on antibiotic treatment failure, and Thurlow, an expert on Staph pathogenesis in diabetes, have long been interested in comparing the effectiveness of antibiotics in a model with and without diabetes. Using their connections within the department of microbiology and immunology, the researchers brought their labs together to perform a study with antibiotics in a diabetic mouse model of S. aureus infection.

First, the team prepared a mouse model with bacterial SSTIs. The mice were divided into two groups: one group was given a compound, streptozotocin (STZ), that selectively kills cells in the pancreas, rendering the animals diabetic, and the other group was not given the compound. Researchers then infected both diabetic and non-diabetic mice with S. aureus and treated the animals with rifampicin, an antibiotic to which resistance evolves at a high rate.

After five days of infection, the authors noticed that the rifampicin treatment had practically no effect in diabetic models. Testing samples the team found that the bacteria had evolved to become resistant to rifampicin, with the infection harboring over a hundred million rifampicin-resistant (RifR) bacteria. The mutation had taken over the entire infection in just four days. In contrast, there were no rifampicin-resistant bacteria in the nondiabetic models. “… we did not detect the emergence of any RifR S. aureus in non-diabetic mice,” the team further noted.

They next inoculated diabetic and non-diabetic models with S. aureus as before, but this time supplemented with a known number of rifampicin-resistant bacteria. While these bacteria rapidly took over the diabetic infection, they remained as only a sub-population in non-diabetic models after four days of rifampicin treatment. “… our data suggest that only in a diabetic environment under antibiotic pressure can this RifR mutant thrive and expand,” the investigators stated.

While the findings have left the team with questions, they maintain that the evolution of antibiotic resistance in people with diabetes could spell trouble for the population at large. Antibiotic-resistant strains of bacteria spread from person to person in the same ways as other bacteria and viruses do—in the air, on doorknobs, and the food that we eat—which makes preventing these types of infections a major priority. “The rapid growth of the diabetic population combined with the concurrent rise of AMR is a serious global health concern,” they noted.

So, what can be done to prevent it? The researchers also showed that reducing blood sugar levels in diabetic models, through the administration of insulin, deprived bacteria of their fuel, keeping their numbers at bay, and reducing the chances of antibiotic-resistant mutations from occurring. “Administering insulin to diabetic mice greatly reduced the emergence of RifR S. aureus … despite only partially restoring normal blood glucose levels,” the investigators stated. Their findings suggest that controlling blood sugar through insulin use could be key in preventing antibiotic resistance. “These data indicate that controlling diabetes with insulin helps to prevent the emergence of antibiotic-resistant S. aureus.”

Conlon added, “Resistance and its spread are not only associated with the prescription of drugs, but also the health status of those that are taking antibiotics. Controlling blood glucose then becomes really important. When we gave our mice insulin, we were able to bring their blood sugar back to normal and we didn’t get this rapid proliferation of resistant bacteria.”

The investigators are expanding their efforts to study the evolution of resistance in humans (with and without diabetes) and other antibiotic-resistant bacteria of interest, including Enterococcus faecalis, Pseudomonas aeruginosa, and Streptococcus pyogenes. Recognizing how large a role the host plays a role in the evolution of antibiotic resistance, the researchers plan to perform similar studies in patients undergoing chemotherapy and recent transplant recipients to see if those populations are also prone to antibiotic-resistant infections.

NanoMosaic published a scientific white paper detailing a study conducted with Bristol Myers Squibb (BMS) that explores the potential of nanoneedle technology as a tool for advancing the understanding of adeno-associated virus (AAV) manufacturing processes and product quality.

During AAV production, natural variations in the viral genome lead to the formation of subpopulations within a single batch. These variations can negatively impact the efficiency of the vector, potentially compromising therapeutic efficacy or causing unintended side effects due to suboptimal AAV subpopulations.

To mitigate these risks, AAV developers and manufacturers implement strategies to selectively enrich preparations with particles containing a complete transgene capable of delivering the desired therapeutic effect.
“The nanoneedle technology offers a unique capability to simultaneously quantify titers of true, full viral genomes as well as a range of partial species, making it an invaluable tool for the next generation of process optimization,” said Daniel Hurwit, senior principal scientist, BMS. “By accurately and quantitatively distinguishing between sub-species of particles and providing a true readout of full-length genomes, the technology enables an improved approach to understanding manufacturing performance and product quality.”

The study demonstrated that the nanoneedle technology can effectively quantify AAV subpopulations, offering critical insights into the production of full-length vectors, according to Hurwit. It also identified pools of partial genomes that may persist in AAV feed streams, addressing major limitations in traditional methods, such as ITR-based tittering, which can misrepresent viral genome content, he continued. “With just two micro liters of sample, this scalable, high-throughput assay can be applied to a wide range of matrices, from crude lysates to purified vectors, enabling more precise monitoring and optimization throughout the AAV manufacturing process,” added Qimin Quan, PhD, co-founder and CSO, NanoMosaic.