New weight-loss drugs are set to overtake Wegovy and Ozempic [Beuzz]

A new class of drugs has revolutionized the way healthcare professionals treat diabetes and obesity. Ozempic, Wegovy and Mounjaro have had spectacular success. Patients using the injectable medications report losing dozens of pounds and controlling their blood sugar in a way unmatched by earlier medications.

But there is still room for improvement. Drug makers are testing new ways to deliver these drugs and developing new ones that may be even more potent.

Eli Lilly is awaiting the green light from the Food and Drug Administration (FDA) to market tirzepatide, sold under the brand name Mounjaro for the treatment of diabetes, as a weight-loss drug. And last month, Novo Nordisk reported that an oral version of semaglutide is as effective in promoting weight loss as Wegovy, the injectable form of the same drug.

Meanwhile, pharmaceutical companies are developing and testing a new generation of experimental weight loss drugs.

“This is a very exciting time for people living with metabolic disease, as well as for scientists and healthcare providers. Where the story will eventually end and what the landscape will look like, I don’t think any of us can predict. The only thing we can say is that the drugs are going to get better and better,” said Daniel Drucker, MD, FRCPCendocrinologist and clinician scientist at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto.

Oral options are on the way

Wegovy, Ozempic and Mounjaro all work by mimicking a hormone called glucagon-like peptide 1 (GLP-1). When a person eats, these GLP-1 drugs signal the body to create more insulin. This lowers blood sugar and delays digestion and appetite, allowing people to feel full longer.

Newer GLP-1 drugs that have been shown to aid weight loss are now only available in injectable form, but that may soon change.

In May, Novo Nordisk announcement that high dose oral semaglutide, which is currently sold as Rybelsus in lower doses for the treatment of diabetes, works as well as injectable Wegovy in helping people lose weight.

On the same day, Pfizer shared mid-stage clinical trial data showing that a new drug, called danuglipron, led to weight loss and blood sugar control over 16 weeks, on par with other agonists. GLP-1. Unlike oral semaglutide, which must be taken one hour before eating or taking other medications, Pfizer’s twice-daily tablet can be taken with food.

Pfizer is also test a once-daily oral drug called lotiglipron in phase 2 trials. The company will see how lotiglipron and danuglipron compare before deciding which one to continue testing in phase 3 trials.

Lotiglipron and danuglipron are considered “small molecule drugs”, while semaglutide and tirzepatide are called “peptide-based” drugs. They work the same way in the body, but small molecule drugs may be more effective oral agents and can be more easily combined with other drugs.

Eli Lilly is also the scholarship an oral GLP-1 agonist called orforglipron.

The development of small-molecule GLP-1 drugs represents “a big breakthrough in the field,” Drucker, who specializes in glucagon-like peptides, told Verywell.

“For people with diabetes and obesity, this is all very good news. This means that in a few years, maybe two to three years, you will have one or more options for taking GLP-1 in small molecule tablet form,” Drucker said. “The more options, the better for people with diabetes.”

There is not enough clinical trial data on these investigational drugs to know how they compare to oral semaglutide. But it is likely that they will be, at least, cheaper. This is because biological proteins are more expensive to create and difficult to scale up production. Pfizer’s small molecule, on the other hand, will likely be easier to mass produce and less likely to experience the shortages seen with Wegovy and Ozempic this year.

Another injectable has the potential to be stronger than Mounjaro

Tirzepatide, currently sold as Mounjaro for the treatment of diabetes, is the most effective drug for promoting weight loss, according to late-stage clinical data presented by drugmaker Eli Lilly. In May, the company applied to the FDA to approve a weight loss indication for the drug.

Like other drugs in this class, tirzepatide works by mimicking GLP-1. But it also acts on a different hormone called gastric inhibitory polypeptide (GIP).

Now Lilly is testing a drug that affects GLP-1 and GIP, and yet another hormone, called glucagon. This so-called tri-agonist, which is currently in mid-stage human trials, may be even more effective than tirzepatide, according to David Lau, MD, Ph.D., director of the Julia McFarlane Diabetes Research Center at the University of Calgary.

In a mouse study, retatrutide promoted greater body weight loss than tirzepatide in obese mice. Animals treated with the drug also seemed to burn more energy than mice given the placebo, despite being under the same calorie restriction.

More obesity management stars on the horizon

None of the currently available GLP-1 agonists rival bariatric surgery – the current gold standard for treating obesity – but they may come close. Drucker said continuing to take medication for the rest of your life can be more painful than a one-time surgery. Still, Lau pointed out that up to a quarter of patients who undergo bariatric surgery see their weight regain, unlike people who adhere to weight-loss drugs.

Studies are ongoing to better understand how drugs in this class stack. For example, Lilly studies tirzepatide face to face semaglutide for obesity. Novo Nordisk, meanwhile, is testing semaglutide at doses up to three times the highest currently approved dose.

The open question is therefore whether a higher dose of semaglutide can compete with the efficacy of tirzepatide. And once new drugs hit the market, how will the next generation of drugs fit in?

“We don’t know yet,” Drucker said. “There are so many different types of combinations being tested, and many of them will be better than what we have so far with semaglutide or tirzepatide.”

Although increasing doses of current and future GLP-1 drugs have made them more effective, the side effects of these high doses may make them unsustainable for most people.

“The main limiting factor for any of these single, double or triple agonists is nausea, vomiting, diarrhea and constipation. If we can overcome these side effects, there are no limits,” said Lau at Verywell.

Some experimental treatments for obesity and diabetes fall out of the GLP-1 class. For example, researchers are testing a once-a-month intravenous treatment that does not reduce body weight, but also increase lean muscle mass.

These advances coincide with a new era in medicine, one that recognizes obesity as a chronic recurring disease, Lau said.

“Drugs like Ozempic and Wegovy have really changed the whole landscape in that we now recognize that obesity is more than just a lack of willpower,” Lau said. “Appetite control is much more complex than simply having the willpower to stop or reduce eating. The discourse “eat less, move more” no longer quite works. »