Diet drug diplomacy and the battle over Greenland
Part one of this article quoted Greenland’s Prime Minister, Múte Bourup Egede, who insisted that his country “will never be for sale.”
Greenland is ours. We are not for sale and will never be for sale. We must not lose our long struggle for freedom.
A week later and Egede has transitioned to being “ready to talk” with the incoming American administration. At a press conference held in Denmark last Friday, he acknowledged Greenland’s strategic importance to the United States, adding,
We have a desire for independence, a desire to be the master of our own house ... This is something everyone should respect. Greenland is for the Greenlandic people. We do not want to be Danish; we do not want to be American. We want to be Greenlandic.
The Danish Prime Minister, Mette Frederiksen, however insisted that “Greenland is not for sale” and currently, the world’s largest island belongs to Denmark. For how much longer?
Sufficient reason to go to war?
While some observers look to historical precedents such as the purchase of Alaska to gain an idea of how much Greenland might cost the US, others wonder whether there will be a price tag attached at all. Superficially, Denmark is a thriving country with a growing economy and no reason to voluntarily relinquish one of its assets, especially when the said asset is extraordinarily rich in natural resources. A glance beneath the surface, however, reveals that Denmark’s economy rests heavily on a single commodity, the GLP-1 agonist semaglutide, better known as Ozempic or Wegovy.
In the United States, this is a source of great frustration for some people, such as Calley Means, who recently posted on X:
First, the Danish people laugh at us by charging 10 TIMES more for US Ozempic than their Scandinavian neighbors pay.
Now, they’re mobilizing their military to defend their dubious Greenland claim.
They are playing us for fools in Denmark and we must no longer stand for it.
Means’ observations are interesting for a number of reasons, not least of which is his recent and very public criticism of using weight-loss drugs to address obesity. Furthermore, the reasons for the high cost of semaglutide in the U.S. are mostly due to American conditions, not Danish price-gouging.
Nor is it clear that the recent increases in defense spending announced by the Danish government are directly linked to Trump’s statements regarding Greenland. Furthermore, the battle over Greenland will likely not be fought militarily, as there are simpler and more effective ways of attacking Denmark.
Stymied by its own success
In December, 2021, Novo Nordisk, the manufacturers of semaglutide, released a statement on drug shortages resulting from overwhelming American demand for the drug:
... Novo Nordisk does not expect to be able to meet demand in the U.S. in the first half of 2022 and few new patients are expected to be able to initiate treatment ... this kink in the U.S. supply chain also isn't expected to be fully resolved until the second half of 2022.
Selling out of the drug was actually very bad news for Novo Nordisk as confirmed shortages triggered the application of a federal law related to such situations. Ordinarily, Novo Nordisk’s products would be protected by their patents, but federal regulations allow special pharmacies called compounding pharmacies to make their own copies if the supply is inadequate to meet national demand. Semaglutide was added to the FDA’s drug shortage list in March, 2022; later that year, so was tirzepatide (Mounjaro/Zepbound, the GLP-1 agonist produced by Eli Lilly).
This was an unusual situation, observed Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists, who told MedPage Today:
It’s a little noteworthy in this case that these are blockbuster, brand-name drugs. Normally, we see shortages of generic drugs.
Safe and effective copies?
A drug produced by a compounding pharmacy is not perfectly identical to the one being copied but it is generally close enough, given that the active pharmaceutical ingredient (API) is purchased from an FDA-registered manufacturer and comes with a certificate of analysis usually based on a drug “master file” handed to the FDA, which contains detailed information on the processing, packaging, and storing of the drug. The pharmacist then crafts the API into dosage form, adding fillers etc., guided by the drug label which provides details of inactive ingredients. (For older drugs, the complete “recipe” is often to be found in the U.S. Pharmacopeia, and sometimes also in scientific journals.)
The drug is then tested to determine the right potency and stability for the formulation. Stabilizers and preservatives are usually added to ensure the correct level of acidity or antimicrobial action. The final step involves sending the drug to an independent laboratory where it is again tested, including for the presence of contaminants.
Although this process can be time-consuming and expensive, the drug ultimately produced is usually substantially cheaper than the blockbuster original version. Accordingly, both Novo Nordisk and Eli Lilly have made extensive efforts to limit the amount of compounded semaglutide and tirzepatide being manufactured, and to discourage consumers from using these cheaper copies. Both companies have filed lawsuits against companies selling compounded drugs; some suits have resulted in sellers being barred from making further sales.
A spokesperson for Eli Lilly told MedPage Today that the company “is deeply concerned that products fraudulently claimed by compounding pharmacies or counterfeiters to be FDA-approved tirzepatide, Mounjaro, or Zepbound, may expose patients to serious health risks.” The FDA does not appear to have confirmed the allegations, although several months ago it did issue a statement relevant to Novo Nordisk, saying that “some” compounded forms of semaglutide might not be based on the same active ingredient as that in the original.
The compounding pharmacies themselves have pushed back sharply against the accusations, insisting that their products are safe and effective. It is important to be aware, however, that compounding pharmacies are not bound by federal reporting requirements of adverse events linked to their products. The agency recently reported that:
The FDA has received reports of adverse events related to compounded versions of semaglutide and tirzepatide. However, federal law does not require state-licensed pharmacies that are not outsourcing facilities to submit adverse events to FDA so it is likely that adverse events from compounded versions of these drugs are underreported...
As of November 30, 2024, FDA has received more than 392 reports of adverse events with compounded semaglutide; more than 215 reports of adverse events with compounded tirzepatide.
Even if compounding pharmacies do provide safe and effective drugs that work exactly as the product they are copying, there are other problems associated with them, such as the relative ease with which those pharmacies prescribe the drug. A recent investigation by Hunterbrook Media, for example, revealed that patients who approached Hims & Hers Health, a pharmacy and telehealth provider, could obtain prescriptions after completing a brief online questionnaire without even speaking to a doctor.
Eli Lilly triumphs
Both semaglutide and tirzepatide remained on the FDA shortage list through 2023 and most of 2024. In October, 2024, however, the FDA stated that the shortage of Eli Lilly’s tirzepatide had been resolved, and the drug was removed from the list. A compounding group promptly sued the FDA, claiming that the drug was in fact still in short supply and that they should continue to be permitted to manufacture and sell it themselves.
In its suit, the Outsourcing Facilities Association called the FDA’s action “arbitrary, capricious and contrary to law,” adding that the federal regulators had unreasonably relied on assurances from Lilly, “a company that is self-interested in monopolizing the market,” that it could meet projected demand.
Survey data from this month show increasing numbers of patients unable to obtain branded GLP-1 agonist products, including specifically branded Tirzepatide products. [Meanwhile, pharmacies and other distributors] continue to list branded Tirzepatide products as out-of-stock or available in only limited quantities.
Nonetheless, after an additional period of deliberation, the FDA again confirmed that tirzepatide was “no longer in shortage” and informed compounding pharmacies that they had 60 to 90 days before the agency began enforcing rules to stop their production of GLP-1 agonist products.
And what of Denmark’s Novo Nordisk?
According to Hunterbrook Media, semaglutide has been listed on the FDA’s website as “available” since October, 2024. Tirzepatide was classified as available 61 days before the drug was taken off the shortage list, which is approximately the average period of time it takes for the FDA to determine that a shortage has been resolved, meaning that patent rights come back into force.
Indeed, in early November, Novo Nordisk announced that it was “on track to make all dose strengths of Wegovy available in the U.S. towards the end of the year.” So far this year they have nearly tripled their weekly U.S. supply, attesting to astonishing demand for the diet drugs. But the FDA has yet to declare the shortage resolved, meaning that cheaper alternatives are still freely available.
Last month, Hunterbrook approached the FDA for an explanation for the apparent delay; the agency replied that,
The FDA cannot provide a general timeline for when a drug may come off the shortage list because each drug shortage is assessed on a case-by-case basis. The FDA continues to actively monitor drug availability and is currently working to determine whether the demand or projected demand for semaglutide within the U.S. exceeds the available supply.
Data supplied by industry figures suggest that millions of prescriptions of Wegovy and Ozempic are being filled per month, while compounding pharmacies are providing less than a quarter of that amount. However, the FDA can delay issuing a declaration that a shortage has been resolved based not only on supply itself but also on supply chain glitches, if it assesses that some parts of the country aren’t receiving sufficient quantities of the drug concerned.
What will happen following the transition of power at the FDA remains to be seen. The incoming administration may be inclined to delay restoring Novo Nordisk’s patent rights over semaglutide. If so, this could be interpreted as pressuring Denmark to be more flexible over Greenland.
Interestingly, the nominee for FDA commissioner, Dr. Marty Makary, serves as an executive officer at the telehealth startup Sesame. Makary may have his own interest in delaying the restoration of Novo Nordisk’s patent protection, as Sesame sells compounded GLP-1 weight-loss drugs. He may, therefore, need to recuse himself from any involvement in the agency's decision.
