Injectable Semaglutide Shortage Forces Physicians to Pivot
As demand for the drug continues to rise, alternatives like the oral formulation and other injectable GLP-1s come into play.
Shortages of injectable semaglutide (Novo Nordisk), sold under trade names Ozempic (for type 2 diabetes with or without established CVD) and Wegovy (for overweight or obesity), are forcing clinicians to look to alternatives when managing patients who need the medication.
Semaglutide and other glucagon-like peptide 1 (GLP-1) receptor agonists have grown increasingly popular in recent years due to their weight loss effects and positive results from clinical trials like SELECT. As a consequence, they might be hard to find in pharmacies.
In a recent post on X (formerly Twitter), Harriette Van Spall, MD (McMaster University, Hamilton, Canada), said that she has switched her patients who were receiving injectable semaglutide to the oral version of the same drug in response to the ongoing shortage in Canada, noting that other GLP-1 receptor agonists—including tirzepatide (Mounjaro/Zepbound) and dulaglutide (Trulicity; both Eli Lilly)—are expected to be in short supply, too.
“Several patients have not been able to access the 1-mg subcutaneous semaglutide pens since around December, and there are shortages of the 0.25-mg and 0.5-mg subcutaneous dosages, too. There are shortages of dulaglutide and tirzepatide also,” Van Spall told TCTMD via email. “Health Canada is advising physicians against initiating these drugs unless there is a clear, evidence-based indication. They are advising physicians to switch their patients to other suitable classes to conserve supplies.”
The issue is not limited to Canada, as the US Food and Drug Administration lists injectable semaglutide, tirzepatide, dulaglutide, and liraglutide (Saxenda and Victoza; Novo Nordisk) as “currently in shortage” due to increased demand. And across the Atlantic, the European Medicines Agency has also put out a notice on a shortage of injectable semaglutide—specifically the Ozempic prefilled pens at doses of 0.25, 0.5, and 1 mg—due to both burgeoning demand and manufacturing issues. The agency said the shortfall is expected to continue through this year. Similar supply issues have been noted for liraglutide (Saxenda and Victoza) and dulaglutide.
We are preferentially prescribing Mounjaro now, or anything but Ozempic because of the supply issues. Darren McGuire
Darren McGuire, MD (UT Southwestern Medical Center, Dallas, TX), told TCTMD the shortage of semaglutide in particular “seems to be quite a big deal.” He noted that he has type 2 diabetes, and after being unable to refill his injectable semaglutide prescription a few times, he switched to tirzepatide. And in his practice, he said, “we are preferentially prescribing Mounjaro now, or anything but Ozempic because of the supply issues.”
McGuire said he personally prefers an injectable option administered once weekly over semaglutide tablets, which are taken daily. He added that patients who have taken an injection previously generally feel that way, too, although there is some hesitation about using injectable therapies.
“We have a lot of patients and a lot of prescribers who have a lot of resistance to an injection therapy,” McGuire said. But those fears are overblown, he said. “You cannot feel the needle enter the skin, so there’s nothing to be afraid of for the injection, and so once people get beyond that issue, I think a lot of people will really enjoy the once-weekly option over taking a tablet every day.”
Indeed, Van Spall said, “the once-weekly dose can be easier to adhere to, so switching to the daily oral dose may require efforts to ensure adherence.”
What to Watch Out for When Switching
Van Spall and McGuire gave some guidance around how to switch patients between therapies if needed. Van Spall said that a patient taking a 0.5-mg subcutaneous injection of semaglutide weekly can be switched to a 7-mg or 14-mg oral daily dose starting within 7 days of the last injection. However, she said, “if several subcutaneous doses have been missed, a starting 3-mg oral dose may need to be initiated with gradual uptitration to avoid GI side effects.”
The tablets “must be taken on an empty stomach first thing in the morning, at least 30 minutes before eating anything else,” Van Spall added. “It is as well tolerated as the subcutaneous version,” which, she noted, “doesn't need to be timed with food or drink.”
When switching from one injectable therapy to another, patients are routinely started on the lowest dose and then uptitrated in order to handle any side effects, with dose adjustments typically occurring every 4 weeks, McGuire said. “Some people have the misconception that if you’re tolerating the maximum dose of semaglutide, you can go straight to the maximum dose of the alternative, and we found when we try to do that, typically people have pretty limiting GI symptoms, sometimes to the point of intolerance.”
If the switch is handled appropriately, patients who’ve been effectively taking semaglutide “will almost certainly tolerate any of the other options,” he said.
Both Van Spall and McGuire advised against use of semaglutide that is being made by compounding pharmacies as a way to deal with shortages of the drug. “Those really make me uncomfortable,” McGuire said. “I just don’t know what’s in those and how they’re formulated and how they’re regulated.”
Patients should be very wary of online programs that offer compounded forms of the drug. Harriette Van Spall
Van Spall said that “patients should be very wary of online programs that offer compounded forms of the drug. Some use salt forms that are not tested for safety or efficacy. These carry a risk of being improperly formulated or inaccurately dosed. In addition, quality assurance standards may not be in place to avoid contamination of the product.”
Although there are multiple options available for patients who require GLP-1 receptor agonists, issues with insurance coverage may complicate any plans to switch from one agent to another, McGuire pointed out, noting that the drugs are expensive. If a patient’s insurance provider will cover only injectable semaglutide and that’s not available, “that kind of forces us into a very difficult situation,” he noted, “because if we prescribe any of the other ones, the person has to pay much more money out of pocket just to get the alternative.”
Clinicians are dealing with issues stemming from these shortages every day, McGuire said. “We’ve had to change what we’re doing.”
The Manufacturer’s Thoughts on Outlook
Asked to comment on the shortages, Novo Nordisk said that it “has made significant investments and has been steadily increasing capacity to produce more Wegovy than ever before. We are enabling more new US patients to initiate treatment by more than doubling the amount of the lower dose strengths of Wegovy into the US market beginning in January of 2024, while gradually increasing overall supply throughout the rest of the year. We expect it will take a couple of weeks for product to arrive in pharmacies.”
The company acknowledged that overall demand will continue to exceed the available supply, “which means that some patients may still have difficulty filling Wegovy prescriptions.”
As for Ozempic, Novo Nordisk said the pens are currently available for patients with type 2 diabetes, adding that it is ramping up production and investing in manufacturing capacity.
“In the US, we cannot control which specific pharmacies or patients receive Ozempic as we distribute our products to wholesalers who in turn supply retail pharmacies nationwide,” the company said. “While we respect every healthcare professional’s clinical expertise and their right to prescribe treatment based on their own medical judgment, we ask that healthcare professionals prescribe our medicines consistent with their FDA-approved indications.”
The company noted that due to rising demand, there will be delays in shipments of Saxenda throughout the year, “which will result in many patients continuing to have difficulty filling their Saxenda prescriptions.”
- McGuire reports consulting for Altimmune, Applied Therapeutics, Bayer, Boehringer Ingelheim, Esperion, Intercept Pharmaceuticals, Lexicon, Lilly USA, Merck, and Novo Nordisk, and serving as trial leadership for AstraZeneca, Boehringer Ingelheim, Esperion, Lilly USA, NewAmsterdam, and Novo Nordisk.