- Wegovy, Ozempic and Mounjaro have been shown to be very effective in helping patients control their type 2 diabetes and lose weight.
- Early data show that drug formulations in the same class, or higher-dose versions of already approved drugs, could be even more potent.
- Some of these experimental drugs can be administered in pill form and may be cheaper and easier to produce than injectables.
A new class of drugs has revolutionized the way healthcare professionals treat diabetes and obesity. Ozempic, Wegovy and Mounjaro have enjoyed spectacular success. Patients using the injectable drugs report losing dozens of pounds and controlling their blood sugar in ways unmatched by previous drugs.
But there is still room for improvement. Drug makers are testing new ways to deliver these drugs and developing new ones that could be even more potent.
Eli Lilly is awaiting the go-ahead from the Food and Drug Administration (FDA) to market tyrzepatide sold under the brand name Mounjaro for the treatment of diabetes as weight-loss drugs. And last month, Novo Nordisk reported that an oral version of semaglutide is as effective at promoting weight loss as Wegovy, the injectable form of the same drug.
Meanwhile, pharmaceutical companies are developing and testing a new crop of experimental weight-loss drugs.
It’s a really exciting time for people living with metabolic disease and for scientists and healthcare professionals. Where the story will end and what the landscape will be like, I don’t think any of us can predict. The only thing we can say is that drugs will get better and better, said Daniel Drucker, MD, FRCPC, an endocrinologist 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, making people feel full longer.
The new GLP-1 drugs that have been shown to promote weight loss are now only available in injectable forms, but that could soon change.
In May, Novo Nordisk announced that high-dose administration of oral semaglutide, currently sold as Rybelsus in lower doses for the treatment of diabetes, works just as well as injectable Wegovy in helping people lose weight.
On the same day, Pfizer shared data from a mid-phase clinical trial showing that a new drug, called danuglipron, led to weight loss and blood sugar control over 16 weeks on par with other GLP-1 agonists. Unlike oral semaglutide, which should be taken one hour before eating or taking other medications, Pfizer’s twice daily tablet can be taken with food.
Pfizer is also testing a once-daily oral drug called lotiglipron in Phase 2 trials. The company will see how lotiglipron and danuglipron stack up 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 drugs. They work similarly in the body, but small-molecule drugs may be more effective oral agents and are more easily combined with other drugs.
Eli Lilly is also researching an oral GLP-1 agonist called orforglipron.
The development of small-molecule GLP-1 drugs represents a major advance in the field, Drucker, who specializes in glucagon-like peptides, told Verywell.
For people with diabetes and obesity, this is good news. It means that in a couple of years, maybe two or three years, you will have one or more options for taking GLP-1 as a small molecule tablet, Drucker said. The more options, the better for people living with diabetes.
There isn’t enough clinical trial data on these investigational drugs to know how they compare to oral semaglutide. But it is likely that at least they will be cheaper. This is because organic proteins are more expensive to create and difficult to scale up. Pfizer’s small molecule, on the other hand, will likely be easier to mass-produce and less likely to experience 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 drug most effective at 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.
As with other drugs in this class, tirzepatide acts 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 now halfway through human trials, may be even more effective than tyrzepatide, according to David Lau, MD, PhD, director of the Julia McFarlane Diabetes Research Center at the University of Calgary.
In one mouse study, retatrutide promoted greater body weight loss than tirzepatide in obese mice. The drug-treated animals also appeared to burn more energy than the placebo-treated mice, despite having the same calorie restriction.
Even more obesity management stars on the horizon
None of the currently available GLP-1 agonists quite rival bariatric surgery, the current gold standard for treating obesity, but they may be close. Drucker said continuing to take medications for the rest of one’s life can be more burdensome than a one-time surgery. Yet Lau pointed out that up to a quarter of bariatric surgery patients see weight regain, while people who adhere to weight-loss medications may not.
Studies are underway to better understand how drugs in this class stack up. For example, Lilly is studying tirzepatide head-to-head versus semaglutide for obesity. Novo Nordisk, meanwhile, is testing semaglutide in dosages up to three times the currently approved maximum dose.
The outstanding question, therefore, is whether a higher dose of semaglutide would compete with the efficacy of tirzepatide. And once the new drugs hit the market, how will next-generation drugs adapt?
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.
While increasing dosages of current or future GLP-1 drugs have made them more effective, the side effects of these high dosages could make them unaffordable for most people.
The major limiting factor of each of these single, dual or triple agonists is nausea, vomiting, diarrhea and constipation. If we can overcome these side effects, there are no limits, Lau told Verywell.
Some experimental treatments for obesity and diabetes are exiting the GLP-1 class. For example, researchers are testing a once-a-month intravenous treatment that doesn’t reduce body weight, but also increases lean muscle mass.
These advances coincide with a new era of medicine that recognizes obesity as a chronic, relapsing condition, Lau said.
Drugs like Ozempic and Wegovy have really changed the whole landscape in the sense that we now recognize that obesity is more than just a lack of willpower, Lau said. Appetite control is much more complex than simply wanting to stop or cut down on your consumption. The eat less, move more narrative doesn’t work anymore.
What does it mean to you
While the future is bright for weight loss drugs, right now only Wegovy can be prescribed on the weight loss label. A healthcare professional can help you figure out if GLP-1 agonists or other treatments are right for you.
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