Why GLP-1 alternatives to Ozempic, Wegovy, Mounjaro and Zepbound can be risky

In only a handful of years, well-known injectable medicines such as Ozempic, Wegovy, Mounjaro and Zepbound have surged into the mainstream, becoming billion-dollar annual sellers used for weight loss, for managing blood glucose, and for lowering the risk of heart disease.

That popularity comes with a significant cost. These injections typically run to around US$800–US$1,000 per month, and when they are taken solely for weight loss, most insurance plans do not cover them.

Both medicines work by imitating GLP-1, a hormone the body naturally produces, helping to control blood sugar and curb cravings. They are only available on prescription.

In 2022, the Food and Drug Administration (FDA) formally announced that the active ingredients used in these medicines were in short supply. However, on 2 October 2024, the agency said the shortage had been resolved for tirzepatide, the active ingredient in Mounjaro and Zepbound.

Even with demand still extremely high and supplies constrained, there are no generic options on the market. The reason is patent protection: semaglutide (the active ingredient in Ozempic and Wegovy, which remains in shortage) and tirzepatide are not due to lose patent protection until 2033 and 2036, respectively.

In the gap left by high prices and limited access, non-brand alternatives-some sold with a prescription and others without-are pouring into the marketplace. These products, however, can pose genuine dangers for consumers.

I am a pharmacist who researches weaknesses in US federal oversight of prescription medicines, over-the-counter products and dietary supplements. My research team has recently examined loopholes that are enabling alternative weight-loss products to reach consumers.

High demand is driving GLP-1 wannabes

Manufacturers in the dietary supplement industry have tried to capitalise on GLP-1 demand by marketing pills, teas, extracts and many other products, often implying they can deliver effects similar to the brand-name injections at a fraction of the cost.

Some products featuring the herb berberine appear to deliver only a few pounds of weight loss. Meanwhile, many supplement weight-loss products have been found to include stimulants such as sibutramine and laxatives such as phenolphthalein-ingredients that raise the risk of heart attacks, strokes and cancer.

The role of compounding pharmacies

In contrast to dietary supplements that present themselves as GLP-1-style weight-loss solutions, compounding pharmacies are permitted to make tailored versions of medicines using the same active ingredients as the brand-name products for patients who, for specific reasons, cannot use a brand or generic product.

These pharmacies may also manufacture alternative versions of brand-name medicines when there is an official drug shortage.

Because demand for GLP-1 medicines has greatly exceeded supply, compounding pharmacies have been legally producing multiple forms of semaglutide and tirzepatide.

Some compounded products differ from the brand-name versions-for example, powder in a vial that must be mixed with liquid, or alternative formats such as tablets or nasal sprays.

As with the brand-name medicines, a valid prescription is required to obtain these compounded versions. Costs generally fall in the US$250–US$400 per month range-still unaffordable for many people.

Compounding pharmacies are required to follow the FDA’s sterility and quality manufacturing standards, but those requirements are less stringent than the rules applied to commercial manufacturers producing generic medicines.

On top of that, compounded products are not required to undergo human testing for safety or effectiveness in the way brand-name products are.

Getting the dose right can also be more difficult with compounded versions of these medicines.

Companies that work the system

For people who cannot pay for a compounded product, or who are unable to obtain a valid prescription for semaglutide or tirzepatide, opportunistic firms have moved in. This includes so-called “peptide companies” that produce non-FDA-approved knock-off versions of the medicines.

Between November 2023 and March 2024, my team conducted a study to identify which of these peptide companies were selling products containing semaglutide or tirzepatide. We searched online for peptide sellers and recorded what they offered as well as how they handled sales.

We found that these sellers rely on a loophole. Their websites commonly claim the products are for “research purposes only” or “not for human consumption”, yet they do not take steps to confirm that purchasers are researchers or that shipments are going to research facilities.

A look at website comment sections and targeted social-media adverts makes it apparent that both buyers and sellers recognise the pretence.

Unlike compounding pharmacies, peptide sellers do not include the supplies needed to mix and inject the drug, do not provide instructions, and typically will not respond to questions.

Because they purportedly are not selling to consumers, these sellers do not ask for a valid prescription and will sell whatever quantity a buyer wants.

Even if someone has an eating disorder such as anorexia nervosa, these companies will still sell them a semaglutide or tirzepatide product without a prescription. Average monthly prices for these peptide products are around US$181–US$203.

Skirting regulations

Peptide sellers are not required to follow the rules and regulations that apply to drug manufacturers or compounding pharmacies. Many claim their products are 99% pure, yet an independent investigation covering August 2023 to March 2024 that tested products from three companies found purity levels well below what was promised.

One product contained endotoxin-a toxic substance produced by bacteria-indicating microbial contamination. The stated dosages were also inaccurate, off by as much as 29% to 39%. Poor purity can lead to fever, chills, nausea, skin irritation, infections and low blood pressure.

The same study reported that some companies never shipped the drug at all, instead telling buyers they had to pay an extra fee for the product to clear customs.

If a consumer is injured by a low-quality product, taking legal action could be difficult because the items explicitly state they are “not for human consumption”.

In the end, consumers are being pushed to spend money on products that may not arrive, could cause infection, may contain the wrong dose, and come with no guidance on how to store or use them safely.

Will prices for brand-name products come down?

In an effort to counter these alternative sellers, Eli Lilly began offering a different version of its brand-name Zepbound for weight loss in September 2024.

Rather than its usual injection-pen products-priced at more than US$1,000 for a month’s supply-this version is supplied in vials, with patients drawing up the dose and injecting themselves.

For patients taking 5 milligrams of Zepbound each week, the vial option would cost US$549 per month if purchased via the company’s online pharmacy and if the patient can demonstrate they do not have insurance cover for the medicine.

Following tough questioning on Capitol Hill in September 2024, Novo Nordisk also faced strong pressure to provide a lower-priced option for patients without prescription coverage for its brand-name Wegovy.

Over the coming years, more brand-name GLP-1 agonist medicines are likely to reach the market. As of October 2024, several were in late-stage clinical trials, including products with active ingredients such as retatrutide, survodutide and ecnoglutide, and more than 18 additional candidates were in earlier development.

As new pharmaceutical competitors enter the field, they will need to undercut Eli Lilly and Novo Nordisk on price to win market share. In the medium term, that is the most likely route to lower GLP-1 drug costs and to end shortages across the marketplace.

• C. Michael White, Distinguished Professor of Pharmacy Practice, University of Connecticut*

This article is republished from The Conversation under a Creative Commons licence. Read the original article.