Anticipating the healthcare reach of GLP-1 receptor agonists

Increasing GLP-1 receptor agonist demand

GLP-1 receptor agonists and GLP-1/GIP dual agonists have been approved for multiple indications, including diabetes and weight management. Although the exact patient eligibility guidelines vary for the drugs in this category, a significant portion of Americans qualify, indicating a high demand. However, most patients eligible for these medications are not on them.

"[Approximately] 42% of Americans have obesity. I don't know what [percentage of the population] is now getting niche therapies, but it's not 42% of the population. It's not even 10% of the population. We are seeing a shift now with niche therapies being prescribed more and more, but we have not penetrated the market yet," noted Caroline Apovian, M.D., professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital.

The physicians on the panel mentioned that the demand for these drugs is significant and continues to grow as the indications expand. However, they noted that despite pharmaceutical manufacturers' efforts, the supply chain for the injection mechanism used for these drugs cannot keep up with the increasing demand.

"When you think about demand today, it's difficult to track because, unlike chronic condition medications where patients get on them and stay on them with some degree of consistency, patients are on and off of these drugs," explained Paul LaViolette, managing partner and COO at SV Health Investors. "If you look at the total number of prescriptions, let's say in 2023, it was probably seven to 9% of the adult population far from the background prevalence of obesity but a significant population, 25 to 30 million prescriptions."

Beyond the significant demand for approved indications, the panelists anticipate an increase as new data proves that these drugs might be useful far beyond diabetes and weight management.

"I was speaking at the National Academies of Medicine on this very topic," revealed Fatima Cody Stanford, M.D., obesity medicine physician-scientist at Massachusetts General Hospital and associate professor of medicine and pediatrics at Harvard Medical School. "They did an entire day looking at the role of GLP-1 agonists for central nervous system conditions, like Parkinson's disease, substance use disorder and Alzheimer's disease."

Although many of these studies are preclinical, clinicians have seen the positive impacts of these drugs on central nervous system disorders among patients who are taking these medications for metabolic reasons. Stanford mentioned that some providers have even noticed a benefit in rheumatologic conditions like gout and rheumatoid arthritis.

"But what this sets us up for is an even greater shortage in demand for these drugs. What we're finding on a day-to-day basis is that we can't get these drugs for patients with metabolic disease. And so as the need for these [medications] rises in these other clinical disorders is that there's going to be greater demand not only here in the U.S., but, we're going to have less and less drug to distribute throughout the population. This will have a greater effect on the population of those most affected by these conditions, which are those marginalized communities," she added.

The cost of GLP-1 receptor agonists

LaViolette mentioned that the cost of these drugs started at $1,100-$1,200 per month and has dropped, hovering around $500. However, that price is still unattainable for many patients who qualify for the medications. LaViolette estimated that 20% to 40% of people are on insurance policies that cover these medications to some capacity. On the other hand, Medicare does not cover these medications at all.

Insurance can be a significant hurdle even when the medication is covered, requiring a lengthy prior authorization process.

"We have hired people to handle all the prior authorizations -- it can take two to six weeks for one patient's prior authorization to go through to get access to the drug, believe it or not," Apovian added.

Across the U.S., those of lower socioeconomic standing will likely suffer the most as demand increases. Access will depend on the patient's ability to afford the medication, which in the U.S. carries a bit of a challenge as the drug pricing landscape is increasingly convoluted. While these medications are extremely expensive in the U.S., they are more affordable in other countries, including those on the U.S. border, such as Canada. At the panel, Stanford told listeners that semaglutide costs approximately $278 per month in Canada, while in the U.S., prices can be as high as $1,600.

"Of course, we have different economics in terms of negotiation for these drugs, and we have to do something better here to ensure that we are accommodating those individuals that are most likely to benefit from these agents here in the U.S.," Stanford emphasized.

Physiological impacts of GLP-1 use

Aside from access and cost challenges, providers have also discussed the different physiological impacts of using GLP-1 drugs, emphasizing that these drugs do not work the same for all patients and may not be the ideal treatment method for some individuals.

"We need to recognize that GLP-1s are not the magical cure. I think we hear often in the media that these drugs will solve obesity or diabetes, but there is heterogeneity in response," explained Stanford. "I see this in my clinical practice all the time. So when I put patients on these therapies, I tell them if they are responders -- if being the keyword there -- then we will continue them on these therapies."

On the other hand, some patients might not be responders, at which point patients shouldn't just stay on the medication because they are portrayed as an ideal solution by popular media.

It is also important to acknowledge that patients' timelines for being on these drugs might differ. Coming off of the medications -- whether that is intentional or unintentional due to cost barriers or prescription drug shortages -- presents a challenge for many patients with regard to weight management. Patients who go off of the medication after achieving weight loss might find themselves regaining the weight and having a more challenging time losing it again.

"Even without medication, when you lose weight through diet and exercise, and then you start to gain it back, and you go back on the diet and exercise, it's harder to lose the weight again initially. There are physiological reasons for that. When you lose weight, as Rudy LeBel discovered in 1995, gut hormones change, and so do fat hormones. All these changes are initiated to get the body to regain the weight because your body has a set point in this environment," Apovian explained. "So it's not about the GLP-1, it's about the body's physiology. So if you stop the GLP-1, which is giving you satiety, that is going to, in some cases, cause hyperphagia, which is a hunger that cannot be satiated very easily, and you regain the weight, and also your total energy expenditure is down."

Compounding GLP-1 drugs

In an attempt to access GLP-1 drugs and circumvent persistent drug shortages or cost barriers, some patients have turned to compounded medications, which present their own set of unique and potentially dangerous challenges.

"Some key players have decided to compound these medications due to shortages. The problem with compounders is that the FDA has found that the compounding medications have not undergone rigorous testing. There are no studies published in any peer-reviewed journals on compounded medications," Stanford noted.

She mentioned that there was a 20% increase in poison control calls with regard to compounded medications. However, compounded versions of GLP-1s are much more readily available.

"The FDA recently ran experiments on several of the compounded pharmacies and found that the agent that they're supplying typically did not even include anything that remotely resembled semaglutide or tirzepatide," Stanford explained, underscoring the dangers of getting compounded GLP-1 drugs.

Although many experts acknowledge the benefits of compounding pharmacies in some instances, several obesity medicine experts and thought leaders are wary of compounding as a solution to GLP-1 shortages and costs.

"When you think about scale in pharmaceutical supply, it's antithetical to think that a hand production compound pharmacy niche is the solution. So, can it emerge locally and provide some solutions, notwithstanding the questions about quality control? Yes. Is that a thematic solution to this overwhelming market demand? I would say very unlikely," LaViolette added.

Despite the dangers of compounded pharmaceutical products, the panelists mentioned that many patients are taking the drugs. Apovian explained that she doesn't prescribe compounded medications, but she has had patients turn to compounded pharmacies out of necessity. In those cases, she advises patients to ensure they get the compounded drugs from a registered pharmacy and that the compound is pure.

Overall, the future of GLP-1 receptor agonists hinges on addressing the many challenges associated with these drugs, including supply chain management, cost, insurance coverage, and beyond.

Veronica Salib has covered news related to the pharmaceutical and life sciences industry since 2022.