diabetes

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Drugmakers can keep making off-brand weight-loss drugs as FDA backpedals

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The judge in the case, District Judge Mark Pittman, granted the FDA’s request, canceling an October 15 hearing, and ordering the parties to submit a joint status report on November 21.

Drugmakers respond

The move was celebrated by the Outsourcing Facilities Association (OFA), which filed the lawsuit.

“We believe that this is a fair resolution in light of the agency’s rash decision to take the drug off of the list at a time when the agency has acknowledged ‘supply disruptions,’ which immediately created a major access issue for patients everywhere,” OFA Chairperson Lee Rosebush said in a statement. “Most important, should the FDA repeat its removal decision when a shortage still genuinely exists, we will return to court.”

The move is also likely to please patients who have come to rely on cheaper, more readily available compounded versions of the drugs. For some, compounded products may have been their only access to tirzepatide.  Still, those drugs are not without risk. The FDA has repeatedly emphasized that compounded drugs are not FDA-approved and do not go through the same safety, efficacy, and quality reviews. And the agency has warned of dosing errors and other safety concerns with compounded versions.

The one party that is certainly unhappy with the FDA’s move is Eli Lilly, which had reportedly sent cease-and-desist letters to compounders. In an emailed statement to Ars, a spokesperson for Lilly said that there was sufficient supply of the company’s drug and continued use of compounded versions is unwarranted. “Nothing changes the fact that, as FDA has recognized, Mounjaro and Zepbound are available and the shortage remains ‘resolved,'” the spokesperson said.

Lilly also noted the FDA’s safety concerns about the compounded versions, adding that its own examination of some compounded products found impurities, bacteria, strange coloring, incorrect potency, puzzling chemical structures, and, in one case, a product that was just sugar alcohol.

“All doses of Lilly’s FDA-approved medicines are available and it is important that patients not be exposed to the risks in taking untested, unapproved knockoffs,” the spokesperson said.

In terms of the supply “disruptions” the FDA mentioned and that some patients and pharmacies have reportedly experienced, Lilly said that the supply chain was complex and there are many reasons why a given pharmacy may not have a specific dose at hand, such as limited refrigerated storage space.

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Buying shady weight loss drugs online is a bad idea, in case you were wondering

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buyer beware —

Risk assessment study of illegal online pharmacies offers some unsurprising data.

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Buying shady weight loss drugs online is a bad idea, in case you were wondering

Buying counterfeit weight loss drugs from illegal online pharmacies that don’t require prescriptions is, in fact, a very bad idea, according to a study published Friday in JAMA Network Open.

The counterfeit drugs are sold as equivalents to the blockbuster semaglutide drugs, Ozempic and Wegovy, which are prescription only. When researchers got their hands on three illegal versions, they found that the counterfeit drugs had low-purity semaglutide, had dosages that exceeded the labeled amount, and one had signs of bacterial contamination.

The three substandard drugs tested came from three different illegal online pharmacies, which sold them as generic semaglutide drugs for weight loss, appetite suppression, diabetes, and cardiovascular health. However, the researchers, led by scientists at the University of California, San Diego, and the University of Pécs in Hungary, had initially tried purchasing counterfeit drugs from six such sellers.

Three of the illegal pharmacies, which specifically sold Ozempic knockoffs, never delivered the drugs after researchers paid for them. Instead, the researchers were hit with “nondelivery” scams, in which the sellers requested additional, hefty payments, supposedly needed to get through customs. These extra fees ranged from $650 to $1,200—much more than what the researchers paid for small dosages of the counterfeit drugs, which ranged from $113 to $360 across the six sellers.

Rogue pharmacies

The Ozempic scams were run out of the rogue online pharmacies: weightcrunchshop.com, puremedsonline.com, and genius-pharmacy.com. The three pharmacies that delivered dubious drugs included semaspace.com, uschemlabs.com, and biotechpeptides.com.

Two of the sellers—semaspace.com and uschemlabs.com—have already received warning letters from the Food and Drug Administration for selling unapproved, misbranded drugs. At the time of publication, the Semaspace website was no longer reachable. The US Chem Labs site was still available, but their semaglutide vials were all listed as out of stock.

The study’s findings, while unsurprising, highlight the risk people may take in efforts to get hold of the popular drugs. Steep prices, lack of insurance coverage, and drug shortages have kept the drugs out of reach for many who could benefit from them. Compounding pharmacies have stepped in to make copycat versions. While these are legal and can come from legitimate pharmacies—ones that are properly registered and require prescriptions—they also carry risks. Compounded drugs are not approved by the FDA and may pose safety and efficacy risks. Last week, the FDA warned of increasing reports of people overdosing on semaglutide products made in compounding pharmacies, leading some patients to be hospitalized.

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People are overdosing on off-brand weight-loss drugs, FDA warns

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Dosage disarray —

Bad math and unclear directions are behind overdoses of up to 20 times the normal amount.

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Wegovy is an injectable prescription weight-loss medicine that has helped people with obesity.

Enlarge / Wegovy is an injectable prescription weight-loss medicine that has helped people with obesity.

The US Food and Drug Administration has approved two injectable versions of the blockbuster weight-loss and diabetes drug, semaglutide (Wegovy and Ozempic). Both come in pre-filled pens with pre-set doses, clear instructions, and information about overdoses. But, given the drugs’ daunting prices and supply shortages, many patients are turning to imitations—and those don’t always come with the same safety guardrails.

In an alert Friday, the FDA warned that people are overdosing on off-brand injections of semaglutide, which are dispensed from compounding pharmacies in a variety of concentrations, labeled with various units of measurement, administered with improperly sized syringes, and prescribed with bad dosage math. The errors are leading some patients to take up to 20 times the amount of intended semaglutide, the FDA reports.

Though the agency doesn’t offer a tally of overdose cases that have been reported, it suggests it has received multiple reports of people sickened by dosing errors, with some requiring hospitalizations. Semaglutide overdoses cause nausea, vomiting, abdominal pain, fainting, headache, migraine, dehydration, acute pancreatitis, and gallstones, the agency reports.

Bad math

In typical situations, compounding pharmacies provide personalized formulations of FDA-approved drugs, for instance, if a patient is allergic to a specific ingredient, requires a special dosage, or needs a liquid version of a drug instead of a pill form. But, when commercially available drugs are in short supply—as semaglutide drugs currently are—then compound pharmacies can legally step in to make their own versions if certain conditions are met. However, these imitations are not FDA-approved and, as such, don’t come with the same safety, quality, and effectiveness assurances as approved drugs.

In the warning Friday, the FDA said that some patients received confusing instructions from compounding pharmacies, which indicated they inject themselves with a certain number of “units” of semaglutide—the volume of which may vary depending on the concentration—rather than milligrams or milliliters. In other instances, patients received U-100 (1-milliliter) syringes to administer 0.05-milliliter doses of the drug, or five units. The relatively large syringe size compared with the dose led some patients to administer 50 units instead of five.

The figure demonstrates how syringe size could lead some to an incorrect dosage.

Enlarge / The figure demonstrates how syringe size could lead some to an incorrect dosage.

FDA-approved semaglutide drugs, meanwhile, are dosed in milligrams and come in standardized concentrations. The agency received several reports of health care providers incorrectly converting from milligrams to units or milliliters, leading them to calculate the wrong dosages. With these math errors, some patients administered five to 10 times more semaglutide than intended.

“FDA recognizes the substantial consumer interest in using compounded semaglutide products for weight loss,” the agency wrote. “However, compounded drugs pose a higher risk to patients than FDA-approved drugs.” The agency urged patients and prescribers to only use compounded versions when absolutely necessary.

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Injection of “smart insulin” regulates blood glucose levels for one week

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Sugary treat treatment —

Tests in animals show the material works like the body’s own system.

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Image of a syringe above three drug vials

Enlarge / Smart insulin has the potential to make injections far less frequent.

People with type I diabetes have to inject themselves multiple times a day with manufactured insulin to maintain healthy levels of the hormone, as their bodies do not naturally produce enough. The injections also have to be timed in response to eating and exercise, as any consumption or use of glucose has to be managed.

Research into glucose-responsive insulin, or “smart” insulin, hopes to improve the quality of life for people with type I diabetes by developing a form of insulin that needs to be injected less frequently, while providing control of blood-glucose levels over a longer period of time.

A team at Zhejiang University, China, has recently released a study documenting an improved smart insulin system in animal models—the current work doesn’t involve any human testing. Their insulin was able to regulate blood-glucose levels for a week in diabetic mice and minipigs after a single subcutaneous injection.

“Theoretically, [smart insulin is] incredibly important going forward,” said Steve Bain, clinical director of the Diabetes Research Unit in Swansea University, who was not involved in the study. “It would be a game changer.”

Polymer cage

The new smart insulin is based on a form of insulin modified with gluconic acid, which forms a complex with a polymer through chemical bonds and strong electrostatic attraction. When insulin is trapped in the polymer, its signaling function is blocked, allowing a week’s worth of insulin to be given via a single injection without a risk of overdose.

Crucial to the “glucose responsive” nature of this system is the fact that the chemical structures of glucose and gluconic acid are extremely similar, meaning the two molecules bind in very similar ways. When glucose meets the insulin-polymer complex, it can displace some of the bound insulin and form its own chemical bonds to the polymer. Glucose binding also disrupts the electrostatic attraction and further promotes insulin release.

By preferentially binding to the polymer, the glucose is able to trigger the release of insulin. And the extent of this insulin release depends on how much glucose is present: between meals, when the blood-glucose level is fairly low, only a small amount of insulin is released. This is known as basal insulin and is needed for baseline regulation of blood sugar.

But after a meal, when blood-glucose spikes, much more insulin is released. The body can now regulate the extra sugar properly, preventing abnormally high levels of glucose—known as hyperglycemia. Long-term effects of hyperglycemia in humans include nerve damage to the hands and feet and permanent damage to eyesight.

This system mimics the body’s natural process, in which insulin is also released in response to glucose.

Better regulation than standard insulin

The new smart insulin was tested in five mice and three minipigs—minipigs are often used as an animal model that’s more physiologically similar to humans. One of the three minipigs received a slightly lower dose of smart insulin, and the other two received a higher dose. The lower-dose pig showed the best response: its blood-glucose levels were tightly controlled and returned to a healthy value after meals.

During treatment, the other two pigs had glucose levels that were still above the range seen in healthy animals, although they were greatly reduced compared to pre-injection levels. The regulation of blood-glucose was also tighter compared to daily insulin injections.

It should be noted, though, that the minipig with the best response also had the lowest blood-glucose levels before treatment, which may explain why it seemed to work so well in this animal.

Crucially, these effects were all long lasting—better regulation could be seen a week after treatment. And injecting the animals with the smart insulin didn’t result in a significant immune response, which can be a common pitfall when introducing biomaterials to animals or humans.

Don’t sugarcoat it

The study is not without its limitations. Although long-term glucose regulation was seen in the mice and minipigs examined, only a few animals were involved in the study—five mice and three minipigs. And of course, there’s always the risk that the results of animal studies don’t completely track over to clinical trials in humans. “We have to accept that these are animal studies, and so going across to humans is always a bit of an issue,” said Bain.

Although more research is required before this smart insulin system can be tested in humans, this work is a promising step forward in the field.

Nature Biomedical Engineering, 2023. DOI: 10.1038/s41551-023-01138-7

Ivan Paul is a freelance writer based in the UK, finishing his PhD in cancer research. He is on X @ivan_paul_.

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