An Ongoing Crisis: Semaglutide Shortage Raises Dual Concerns for Obesity and Diabetes Treatment

Between celebrity endorsements, before-and-after TikToks, and the increasing evidence of its weight-loss benefits, it is no surprise that the rapidly growing popularity of semaglutide as a weight loss tool has led to a nationwide shortage of the glucagon-like peptide 1 (GLP-1) receptor agonist.

But what does this mean for patients who are finding it more and more difficult to access this drug?

Ozempic injection | Image credit: mbruxelle – stock.adobe.com

Semaglutide is sold under the brand names Ozempic, Rybelsus, and Wegovy—all manufactured and sold by Novo Nordisk. Ozempic injection and Rybelsus tablets are FDA approved as a supplement to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D).¹ Meanwhile, the 2.4 mg Wegovy injection is indicated for weight loss for individuals with overweight or obesity with a body mass index (BMI) of at least 27 kg/m² and at least 1 weight-related complication, or a BMI of at least 30 kg/m².² While Wegovy can benefit patients with T2D through weight management, it is not meant to directly treat T2D in the same way as Ozempic and Rybelsus.

Despite the different indications, people have been using Ozempic and Rybelsus for weight loss, which has contributed to decreased access for patients with T2D who need it to manage their condition.³ An analysis of electronic health records shared with CNN by Epic Records estimates that around 1.7% of all Americans have been prescribed a semaglutide medication in 2023 alone, reflecting a nearly 40-times increase over the past 5 years.³ Additionally, the increased popularity of Wegovy is making it harder for patients with overweight or obesity who have been using it for weight loss to access the treatment that has been working for them.

According to data collected between 2017 and 2020, 41.9% of US adults have obesity, and nearly 20% of American children and adolescents have obesity.⁴ Zoomed out, the World Health Organization (WHO) estimates that more than a billion people have obesity worldwide, including 650 million adults, 340 million adolescents, and 39 million children.⁵

Trends in Weight Loss Drug Use

According to data published in the 2023 Trends Shaping the Health Economy Report in September, national spending on semaglutide reached a total of $10.7 billion in 2021, making it the fourth highest across drug classes in terms of spending.⁶

Ozempic is also the most prescribed GLP-1 receptor agonist.⁶ In Q4 of 2022, health care providers in the United States wrote more than 9 million prescriptions for semaglutide, tirzepatide (Mounjaro), and liraglutide (Saxenda) in just 3 months, with semaglutide accounting for around 7 million of these prescriptions. With the May 2022 approval of tirzepatide for T2D and its increasing use among patients without diabetes looking to manage their weight, there is potential for it to eventually take the spot Ozempic currently holds. On the other hand, liraglutide was found to be less effective for weight loss compared with the other 2 drugs, leading to a slow decline in use.

Across major markets, there has been a rise in the count of individuals using Ozempic who have a background of overweight, obesity, or experiencing other forms of hyperalimentation, according to the report. This surge varies, showing an increase of 48% in Minneapolis, Minnesota, to as much as 481% in Cleveland, Ohio.⁶ The prevalence of both on-label and off-label usage also differs across various markets.

“From 2020 to 2022, the quarter-over-quarter percent change for GLP-1 prescriptions has increased but the rate of future utilization will depend on manufacturer supply, cost and prioritization of on- and off-label use,” the report said. “Notably, just over half of patients taking these medications have a history of type 2 diabetes or have an associated medical visit with their prescription.”

How Do Celebrity Endorsements Contribute to the Uptake Boom?

According to People, household names like Oprah Winfrey and Tracy Morgan have used and encourage the use of semaglutide for people who are overweight or obese who feel like nothing else has helped them take off and keep off the weight.⁷ On the other hand, Sharon Osbourne and Amy Schumer are among those who have used the drug for that purpose and have regrets around it, including losing more weight than expected and generally feeling unwell. Meanwhile, actor Anthony Anderson noted how the drug’s increasing use for weight loss negatively impacts people like him who are living with T2D, telling People, “It's creating a shortage for those of us who need the medicine that we need and not for weight loss issues, but for our health.”

Anderson’s statement aligns with what others with T2D are experiencing when trying to access Ozempic, as opposed to the rich and famous who can access these treatments much more easily.

Many patients with T2D are experiencing challenges in getting reimbursed for drugs like Ozempic due to US insurers implementing restrictions to discourage prescribing the medication for weight loss.⁸ Novo Nordisk acknowledged tighter health plan management of GLP-1 drugs, contributing to a recent decline in US prescriptions.⁹ Patients have reported delays and obstacles, including prior authorization requirements and the need to try alternative medications, which raises concerns about potential impacts on diabetes management and overall health outcomes.

In fact, these issues did not just start this year, as Ozempic became a celebrity weight loss sensation back in 2022.¹⁰

Marketed as a potential solution to the obesity epidemic, Ozempic gained public attention after being featured on The Dr. Oz Show in an episode from February 2021.¹¹ Initially approved by the FDA for diabetes treatment in December 2017, the higher-dose form, semaglutide 2.4mg, branded as Wegovy, was later approved for weight loss in June 2021. Elon Musk's Twitter endorsement of "fasting and Wegovy" on October 1, 2022, further intensified interest.¹² However, a shortage of Wegovy—which was put on the FDA’s drug shortage list in March 2022—led health care providers to prescribe Ozempic for weight loss as an alternative.

Using Semaglutide for Weight Loss

To learn more about what patients and physicians are experiencing amid this shortage, The American Journal of Managed Care^® (AJMC^®) spoke with Ian Neeland, MD, director of cardiovascular prevention and co-director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease, University Hospitals Harrington Heart & Vascular Institute, and associate professor of medicine at Case Western Reserve University School of Medicine.

Neeland mentioned a noticeable increase in interest in semaglutide for weight loss in his practice over the past year, noting that, as a cardiologist, he doesn’t specifically work in chronic weight management but gets a lot of patient referrals for it as cardiovascular health and weight are often linked. In general, he will often start the patient on a GLP-1 receptor agonist if it is indicated for the treatment of obesity. However, it can be a difficult conversation to have with the patient when insurance does not cover chronic management for these medications, causing them to have to pay out of pocket.

“Some of my patients are well-to-do and can afford that cost, [but] many others cannot,” Neeland said. “It's unfortunate because we have something to offer individuals but many times they can't get it, and not because of the shortage per se, just because of the cost of the medication. Certainly, over time with more options in the market, those costs will likely come down and as things go generic, but for the meantime, it can be a difficult conversation to have with patients that we have effective medications, but I’m not sure you can utilize it because you can't necessarily afford it or that insurance will cover it.”

When patients with overweight or obesity seek assistance for weight loss, Neeland described a comprehensive evaluation involving a thorough examination of medical history and potential indications or contraindications for GLP-1 receptor agonists, emphasizing the importance of counseling and education about potential side effects, and addressing concerns and offering strategies to mitigate these effects. University Hospitals has a pharmacist-led dose escalation protocol, as Neeland explained, emphasizing the pharmacist's role in assessing side effects and ensuring a smooth transition to higher doses. This approach aims to facilitate patients' progress toward the maximum tolerated and most effective dose, tailored to individual needs.

It’s also important to know that not everyone will respond to semaglutide for weight loss, and guidelines for the treatment of obesity include other approaches for those who may need them.²

If patients using semaglutide are not experiencing weight loss within a specific timeframe, the decision to discontinue the medication depends on the underlying reasons for the lack of efficacy. According to Neeland, if the achieved dose is deemed insufficient, dose escalation might be considered as an option, or if individuals show a limited response to this particular medication, switching to a different GLP-1 receptor agonist could be a suitable alternative. Additionally, modifying dietary habits and lifestyle behaviors may be essential for optimizing weight loss outcomes. The course of action depends on the context, and the conversation about discontinuation involves exploring various factors influencing the patient's success on the medication, with the option to switch to an alternative agent if deemed beneficial.

How Does the Shortage Affect Individuals With Diabetes?

When it comes to helping his patients with T2D navigate their diabetes management during the shortage, Neeland said there is no one-size-fits-all approach, but there are steps he takes to help patients avoid going completely off semaglutide. This includes reducing the dose to the next available dose, trying to access the drug through other pharmacies, or getting the drug out of country. It’s important to note that semaglutide works by uptitrating the dose, so when patients with diabetes have their regimen interrupted or disrupted completely for a long period of time—even as little as 2 to 3 weeks—due to these shortages, that’s when there are concerns for the patient’s ability to maintain glycemic control. When this happens, patients typically have to start over from the lowest original dose and escalate doses all over again, since stopping the regimen and going back to a higher dose commonly leads to adverse events, and patients may have reduced glycemic control during this time.

Neeland also mentioned that there is an oral semaglutide option that is not currently experiencing shortages and is indicated for diabetes management. The pills have not been tested for a weight loss indication, which he said is likely why patients looking to lose weight are not asking for them instead of the injection, but they are a good alternative for when patients with diabetes are having trouble accessing the injection.

Oral semaglutide has a few limitations not present in injectable semaglutide. First, it requires daily administration compared with the once-weekly injectable form. Additionally, it must be taken with minimal water and without any other medications or food, making the timing of ingestion potentially challenging. This could pose adherence difficulties, especially for individuals who prefer a more structured morning routine or struggle with coordinating multiple medication schedules. Further, there are essentially 3 fixed doses for oral semaglutide, whereas the injectable form offers a bit more flexibility in dosing.

Despite these considerations, oral semaglutide remains a viable and effective option, particularly for managing T2D and, depending on whether future clinical trials test for this and yield positive results, potentially for off-label use in weight loss.

The Role of the Employer

In an interview with AJMC, Dawn Weddle, vice president of the Midwest Business Group on Health (MBGH), was frank on her views of the semaglutide shortage.

“From an employer perspective, we feel that the priority should always be given to patients that have diabetes and not necessarily being used just for weight loss, especially when there are shortages,” she said.

Weddle explained that employer plans typically do not cover off-label drug use, making it challenging for individuals to obtain Ozempic for weight loss. The national shortage seems more pronounced in higher-dose pens used for severe cases diabetes, creating concerns for patients who rely on these medications. While manufacturers are working to address the shortage, challenges with the supply of plastic pens persist, and the FDA approval process for manufacturing new pens adds complexity to resolving the issue.

In a recent learning network event by MBGH titled "Obesity, the Employer Conundrum," a session focused on how employers make informed decisions regarding the coverage of GLP-1 weight loss medications, with a particular emphasis on semaglutide as the most prescribed GLP-1. The discussion highlighted the evolving scientific understanding of obesity, emphasizing the shift from solely lifestyle interventions to recognizing obesity as a chronic condition. The featured expert, a registered dietitian, emphasized the effectiveness of GLP-1 medications in helping employees manage their weight, stressing that treating obesity as a chronic condition requires a long-term approach.

The session acknowledged the conundrum employers face in navigating the challenges of covering GLP-1 medications. Employers recognize the efficacy of these medications in weight management and understand the broader impact on various health conditions associated with obesity. However, the high prevalence of obesity in the workforce, affecting nearly 70% of the population, poses a considerable challenge. The lack of a standard of care for obesity adds complexity for employers, who must determine appropriate guardrails for medication use. Various strategies, such as BMI thresholds, comorbidities, pre-authorizations, and directing employees to specialized medical centers, were discussed as potential approaches to ensure the right medication reaches the right patient at the right time.

“I think one of the reasons that [using diabetes drugs for weight loss] has become so popular is, number one, they're effective,” Weddle said. “There have been other medications out there for a long time, other anti-obesity medications that are pretty cheap, they’re less than $100 a month, but they don't even come close to the results of Wegovy in terms of weight loss. Patients on Wegovy are seeing a 15% reduction in their weight and, and these other anti-obesity medications aren't even coming close to that.”

How Will the Shortage Carry Into 2024?

The semaglutide shortage issue has gained significant mainstream attention throughout 2023, prompting Novo Nordisk to increase funding to enhance production capacity. On December 12, 2023, Novo Nordisk released a statement, addressing the shortage of specifically the Wegovy 1.7 mg dose in the United States, saying it expected to resume shipments in early January 2024.¹³

Despite these efforts, though, shortages are expected to persist into the next year, and new data highlighting the positive cardiovascular benefits of Wegovy adds complexity to the situation and raises concerns of continued or even worsened shortages. Looking ahead to 2024, Neeland and Weddle both expressed hope for changes to mitigate shortages and ensure the drugs reach those who need them the most.

While manufacturer supply issues are being addressed, the broader supply chain—including shortages of pens—remains a challenge. Weddle noted that medium and large employers are more likely to cover these medications, and the hope is that increased market competition will eventually lead to lower prices. Encouragingly, the potential for primary care physicians to receive training in obesity management was highlighted as a crucial aspect. Having more clinicians trained in prescribing these medications appropriately is essential to ensure they are used correctly, ultimately reducing the risk of shortages and promoting successful outcomes for patients.

References

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9. Beasley D. Focus: US diabetes patients face delays as insurers tighten Ozempic coverage. Reuters. December 13, 2023. Accessed December 20, 2023. https://www.reuters.com/business/healthcare-pharmaceuticals/us-diabetes-patients-face-delays-insurers-tighten-ozempic-coverage-2023-12-12/
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