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New drugs on the market for treating type 2 diabetes and obesity, including popular drugs like Ozempic and Wegobee, are more effective at helping you lose weight than any of its predecessors, but doctors and researchers are still making progress. says there is room for
Next-generation options currently in development may be easier and more convenient to consume, promote weight loss, and provide additional health benefits.
“This is all really good news,” said Dr. Louis Aronne, director of the Center for Comprehensive Weight Management at Weill Cornell Medicine. “We need drugs that do different things.”
Some state-of-the-art experimental drugs can be taken in pill form rather than by injection. Ozempic and Munjaro, currently approved for type 2 diabetes, and Wigobee, a weight-loss drug, are all administered as self-injectors once a week.
Novo Nordisk, which makes Ozempic and Wegoby, markets a daily tablet version of the same drug called semaglutide, which is approved for diabetes and is being tested at higher doses for weight loss.in the later research result The drug, announced this week, was found to help people lose 15% of their weight over 68 weeks, compared with 2.4% for those who took a placebo.
Novo Nordisk said the results, which have not been published in a peer-reviewed journal, were similar to the weight loss seen with the injectable Wegobee. Side effects were similar, the company said. Gastrointestinal problems such as nausea and diarrhea are most common with this class of drugs known as GLP-1 analogues. Novo Nordisk said “the vast majority are mild to moderate and diminish over time.”
The company plans to apply for regulatory approval in the United States and Europe this year, and said availability would depend on its drug’s priorities. And about manufacturing capacity. Wegobee is now being distributed to some patients because demand is outstripping supply.
But despite being available in tablet form, oral semaglutide, marketed under the brand name Libersus for type 2 diabetes, can still be complicated to take, doctors say.
“Patients taking Libersus should be instructed on strict requirements before and after oral administration,” said Priya Jaishingani, Ph.D., an endocrinologist and obesity medicine expert at New York University Langone Health. . She can’t eat or drink anything other than 4 ounces of water or take other medicines within 30 minutes of taking the medicine or it may weaken the effects of the medicine. Stated.
Other oral GLP-1 drugs are in development that can be taken with food, including two from Pfizer.The company published data This week in JAMA Network Open, we published a paper on the use of a twice-daily tablet called danugliprone in people with type 2 diabetes. A mid-term study found that the drug lowered blood sugar levels and led to weight loss at high doses for 16 weeks, which the researchers said was comparable to other drugs in this class. So were the side effects.
Pfizer is developing a second experimental drug designed to be taken orally once daily. The company plans to select one of its drugs to move into late-stage clinical trials for both diabetes and obesity, which is scheduled to begin next year.
About 24 other experimental drugs designed to be taken to treat obesity and related conditions are currently in development, according to a study by financial firm TD Cowen.
“For most people, of course, pills would be more appealing,” says Dr. Wira Xue, director of the Center for Diabetes and Metabolism Research at The Ohio State University Wexner Medical Center. In addition to avoiding injections, the tablet version may be more effective if you need to stop taking the drug because of side effects, she noted. If a certain level of weight loss is reached with injections, the tablets may also help with weight maintenance, she said.
But Hsueh also noted that “some patients may prefer weekly injections to pills, especially if they are already taking several daily.”
Injectable drugs are also being developed, many of which seek to exceed the weight loss seen with currently available options.
Lilly’s tirzepatide, approved as Mounjaro for type 2 diabetes, reportedly produced 21% weight loss at the highest dose in a 72-week clinical trial for obesity. result It was published last year in the New England Journal of Medicine.
The drug is expected to receive FDA approval for weight loss in people without diabetes either this year or early 2024. The drug builds on the 15% weight loss seen with Wegovy by adding a target called GIP in addition to GLP-1.
“Semaglutide has a GLP-1 effect, and tirzepatide has dual effects, GIP and GLP-1, resulting in greater weight loss.” [in] Some next-generation drugs have triple effects,” said Aronne of Weill Cornell University.
One of these drugs, also in development at Lilly, targets a target called glucagon in addition to GIP and GLP-1. Aronne, who has been an attending physician in obesity clinical trials and has consulted for companies developing weight-loss drugs, calls it the “triple G.”
“This seems to be more than a 25% weight loss,” Aronne said.
Lilly said he plans to begin late-stage trials of the drug, called letartortide, this year.
If successful, it could compete with Novo Nordisk’s combination known as Kagrisema. Kagrisema combines semaglutide with a compound called caglilintide, which works by stimulating a hormone called amylin, leading to additional weight loss.
“We will continue to develop more effective treatments,” Aronne said.
Other drugs in development are aimed at improving fat loss in the liver and could be useful in diseases such as non-alcoholic steatohepatitis, Aronne said, but they are less likely to cause liver failure and transplants. major cause of need. Another experimental drug targets receptors in muscle to prevent loss of lean body mass as part of overall weight loss.
It can take many years for many of these drugs to hit the market. Some may fail in clinical trials. However, progress in this field is rapid, and some experts see current therapies as just the beginning of a renaissance in drug discovery for weight management and related applications.
“We’re still in the first inning,” said Raymond Stevens, CEO of the biotech company. Structural Therapeutics, working on oral GLP-1. “We’re still learning a lot about exactly how to dose drugs and how much weight to lose in a particular individual. So it’s still early days.”
Oral drugs may offer the option of titrating or increasing the dose over time, which doesn’t cause as many gastrointestinal side effects as injections do, Stevens said. rice field.
Ohio State University’s Xue noted that 5% to 10% of patients cannot tolerate the nausea, vomiting and other side effects that currently available drugs can cause.
But the first thing she needs to improve on medicines, she said, is insurance coverage. Many insurers, she said, consider weight loss to be cosmetic and deny coverage for medicines costing more than $1,000 a month.
A successful clinical trial, which is expected to yield results this summer, could change that, Aronne said. Novohis Nordisk says semaglutide has already shown a protective effect in people who are overweight or obese but he doesn’t have type 2 diabetes, and Wigobee reduces the risk of heart disease and stroke. I’m testing if it helps.
“I think it’s very important,” Aronne said, to test the extent to which these drugs are effective in protecting health. “I’m very excited that we’re getting to this point.” .
