Within the first 5 seconds, Recent Ozempic commerciala sky blue injection pen, surrounded by a large red pen, rolls towards the viewer. ○. Obesity drugs are so closely related to injections that the two are virtually synonymous. Like Ozempic, whose name is now an umbrella term for obesity drugs, Wegovy and Zepbound come packaged in Sharpie-like injection pens that patients self-administer once a week. Laura Davison, a professor of medical weight management at West Virginia University, told me that patients “don’t come looking for Wegovy.” “They come looking for ‘that shot’.”
The needle is in the present, but perhaps not in the future. No one likes injections, and it’s much easier to take a pill. In a frenzy over obesity drugs known as GLP-1 agonists, drug companies are racing to develop them in pill form and Wall Street investors are I’m hungry In perspective. Earlier this year, Pfizer CEO Albert Bourla said: Estimation Obesity drugs could be worth $30 billion, or one-third of the entire obesity drug market. He told the conference that pills would eventually “unlock the market” for obesity drugs because people “prefer” them.by one countat least 32 oral GLP-1 drugs are being developed by various companies.
However, it is far from certain that the future will be dominated by obesity drugs. So far, the only oral GLP-1 in existence is a diabetes pill called Libersus. Like Ozempic and Wegovy, its active ingredient is a compound called semaglutide, but the shot’s dosage is much more potent and can lead to even more weight loss. Developing oral obesity treatments that are as well tolerated and effective as injectables has thus far been a challenge. early this month, Pfizer has halted trials on one of its pill candidates, citing concerns about side effects and patient compliance. Doctors said there is no guarantee that people will flock to the pill even if it comes to market.
It is no surprise that pharmaceutical companies consider the injectable nature of GLP-1 to be one of its biggest flaws. Receiving an injection is a widely despised experience, one that people generally tolerate rather than choose. Children receive stickers when they continue their vaccinations. Adults who get vaccinated do so simply because they have to (and often receive a sticker as a reward). The CDC estimates that 1 in 4 adults and 2 in 3 children have a girlfriend. strong fear of needles. “Some people don’t like needles, plain and simple,” obesity policy expert Ted Kyle told me.
But not all needles are created equal. Wegovy and Zepbound are injected subcutaneously, just under the skin. It’s less uncomfortable than a coronavirus or flu shot, which is shot into the muscle. “I’m really surprised at how accepting my patients are of using injectable drugs,” Davison said. Other doctors I spoke to agreed. “More patients than you might expect actually have no aversion to injectable drugs,” said Katherine Saunders, a professor of clinical medicine at Weill Cornell University. This is because injections are easy to administer and relatively painless.
The injectable’s discreet dosing schedule further enhances its appeal. Wegovy and Zepbound are administered once a week, unlike many tablets in development that are meant to be taken more than once a day. It can be a hassle, especially if you have to take it at the same time every day or have restrictions on what you can eat and drink. “For some people, it’s easier to get a shot and forget about it for a week than to remember to take a pill every day,” said Eduardo Grunwald, an obesity physician at the University of California, San Diego. It’s an “unnatural reaction” to think a pill is better than a shot, he added.
Despite the shot’s unexpected benefits, it’s far from perfect. Manufacturing injectable pens is generally more expensive than tablets and requires more capital. hardware, includes a pencil case, cap, and needle cover. Additionally, injectable obesity drugs must be refrigerated before first use, increasing storage and manufacturing costs. Tablets are usually shelf-stable and require little packaging other than a pediatric bottle. Sanders predicts those products will be cheaper and less prone to the shortages plaguing Wegovy.
Still, making an obesity drug is not as simple as packaging the same drug in capsule form. Pharmaceutical companies already face many problems. Absorption is important. Tablets pass through the stomach before entering the bloodstream, so they must be able to withstand significant degradation. One way to achieve greater weight loss with these drugs is to increase the dose. The highest dose for Wegovy is 2.4 milligrams, while the highest dose for Rybelsus is 14 milligrams.
Increasing the dose seems to help, but doing so can have effects beyond weight loss. All GLP-1 drugs come with a variety of unpleasant gastrointestinal side effects, and patients complain of nausea at similar rates with Libersus and Ozempic, according to the FDA. However, this may actually be different. other doctors he pointed out. Sanders said patients receiving oral semaglutide report more nausea than those using the injectable drug. In any case, new oral drugs may have even more distinct differences as drug companies race to develop more powerful pills.Pfizer’s canceled trial of Danuglipron had high rates of nausea reached up to 73%.
Pharmaceutical companies are also circumventing the problem of degradation by pursuing more powerful drugs. The problem with semaglutide is that it is a peptide (essentially a small protein), which is exactly the type of molecule that the stomach is good at digesting. Some new drugs in the pipeline are so-called non-peptide small molecules, which are more robust but still have the same biological effects.Orforglipron, Eli Lilly tablets test, as well as Danuglyprone, the drug responsible for Pfizer’s recent setback, fall into this category. Small molecule drugs also have the following advantages: cheap Kyle, the obesity policy expert, added that they would need to be produced on a larger scale than peptides.
Another thorny issue with oral medications is that they tend to have strict dosage requirements. people above LibersusFor example, you are instructed to take it 30 minutes before eating or drinking anything, and all you can drink with it is 4 ounces of plain water. Because otherwise absorption may be impaired. “That can be a nuisance,” Grunwald said.Similarly, cumbersome instructions have a lower dropout rate. 50 percent In Pfizer’s recently discontinued trial, danuglyprone had to be taken twice a day. “Many people decided it wasn’t worth the trouble,” Kyle said, noting that Pfizer is still pursuing a once-daily version of the same drug.a recent reviews GLP-1 drug studies showed lower rates of reported side effects with oral semaglutide compared to injectables; taller than Discontinuation rates may reflect its onerous dosage requirements.
Despite these hurdles, it seems inevitable that obesity drugs will eventually become available.Novo Nordisk plans to apply to FDA for approval of high-dose semaglutide obesity treatment this year; Pfizer is developing a once-daily version of danuglipron and expects to have more data “in the first half of 2024,” a spokesperson said.a report A BMO Equity Research paper published in September predicted that an oral formulation could be approved “by the late 2020s.” The biggest advantage of a pill may not be that it’s a pill, but that it becomes a pill. Finally, cheaper than injectables. And the cost is one of the biggest obstacles to getting more people to take obesity drugs.
It is by no means certain that they will completely replace injectables. “Ultimately it will depend on patient preference,” Grunwald said. Perhaps tablets and injections will coexist to meet different needs, perhaps even being used together to treat individual patients.So-called step-by-step approach, obesity treatment may start with more expensive and powerful injectable drugs and then move to less powerful but cheaper oral drugs in the long term. For example, Eli Lilly has announced that its oral candidate, orforglyprone, Possibility of weight loss maintenance drugs.
Due to the intense competition in the field of obesity drugs, future treatments may take even more unexpected forms. Amgen is injection once a month; Novo Nordisk is developing Semaglutide in hydrogel form It only needs to be taken three times a year. If the future of obesity drugs depends on patient preference, the more options the better.
