Experimental drugs aim to surpass weight-loss stars like Ozempic and Wegovy

CNN

Doctors and researchers agree that the new generation of medications for obesity and type 2 diabetes, such as Ozempic and Wegovy are more effective than previous drugs at reducing weight, but they say there is still room for improvement.

The next-generation products, which are currently being developed, may be more convenient and easier to use. They could also offer greater health benefits and help you lose weight faster.

'This all is really good news', said Dr. Louis Aronne of Weill Cornell Medicine's Comprehensive Weight Control Center. We need different drugs.

Some of the most innovative experimental drugs can be taken as pills rather than injections. Ozempic, Mounjaro and Wegovy are approved to treat type 2 diabetes and are given by self-injection once a week.

Novo Nordisk (which makes Ozempic, Wegovy and other drugs) has a daily dose of semaglutide that is approved for diabetes. It's also testing a higher dosage for weight loss. The drug helped people lose 15 percent of their body weight in 68 weeks. This is compared to 2.4% among those who took a control.

Novo Nordisk stated that the results were similar to those seen with Wegovy injections. The results have not been published by a peer reviewed journal. The company also said that the side effects were similar; nausea and diarrhea, which are common gastrointestinal problems, are more prevalent with this class, called GLP-1 analogs. Novo Nordisk stated that the "vast majority" of side effects were mild to moderate, and decreased over time.

The company plans to apply for regulatory approvals in the US and Europe by this year. Availability will depend on its priorities and manufacturing capacity. Wegovy, which is being rationed at present for some patients due to a shortage of supply, has been rationed.

Doctors say that despite being in tablet form, oral Semaglutide, sold as Rybelsus, for type 2 diabetics, can be difficult to take.

Dr. Priya Jaisehani, endocrinologist at NYU Langone Health and an expert in obesity medicine, said that patients taking Rybelsus must be informed of the strict requirements to follow before and after oral administration. She said that they can't drink more than 4 ounces water, eat or take any other medicine within 30 minutes after taking the drug.

Pfizer is developing two other oral GLP-1 medications that can be taken along with food. This week, the company published in JAMA Network Open data on a twice daily pill called danuglipron for people with type 2 diabetics. In the midstage trial, researchers found that the drug lowered blood glucose and caused weight loss when taken at higher doses for 16 weeks. This was similar to other drugs of the same class. The side effects were similar.

Pfizer is developing a second experimental drug, lotiglipron. It's meant to be taken once daily orally. The company will choose one of these medicines to move forward into late-stage trials for both diabetes and obesity. These are expected to begin next year.

According to TD Cowen's research, there are nearly two dozen more experimental drugs in development for the treatment of obesity and other conditions.

'A pill would, of course be more appealing to most people', said Dr. Willa Hueh, Director of the Diabetes and Metabolism Research Center of Ohio State University’s Wexner Medical Center. She noted that, in addition to the fact that they avoid injections, pills could also be more convenient if a person needs to stop taking a drug due to side effects. She said that a pill may be useful for maintaining weight once a person has reached a certain weight loss with injectable drugs.

Hsueh pointed out, however, that some patients prefer an injection once a week to a pill. This is especially true if the patient already takes a few pills daily.

Many injectable drugs are being developed to help achieve greater weight loss than the current options.

According to results published in the New England Journal of Medicine last year, Eli Lilly’s tirzepatide (marketed as Mounjaro for type 2 diabetics) led to a weight loss of 21 % at the highest dosage over a 72 week clinical trial on obesity.

FDA approval is expected this year or early in 2024 for the drug to be used in weight loss by people without diabetes. The drug builds on Wegovy's 15% weight loss by adding GIP, a new target to GLP-1.

Aronne from Weill Cornell said that the next generation will include drugs with three effects.

Another medication, in development by Lilly, targets glucagon as well as GIP and GLP-1. Aronne, a primary investigator in obesity clinical trials, and a consultant for companies developing weight-loss drugs, refers to it as 'triple G'.

Aronne stated, 'That's seems like it will go beyond 25% of weight loss'.

Lilly expects to begin late-stage clinical trials for the drug, retatrutide this year.

If the drug is successful, it could compete with CagriSema from Novo Nordisk, which combines semaglutide with cagrilintide, a compound that stimulates a hormone known as amylin in order to cause additional weight loss.

Aronne stated that 'we're going have more treatments which are even more efficient'.

Aronne stated that nonalcoholic steatohepatitis is a leading cause of liver failure, and the need for liver transplants. Other drugs are still in early development, but aim to reduce fat in the liver. Another experimental drug targets the receptor in muscle tissue to prevent loss of lean body mass as part overall weight loss.

Many of these drugs could take years to reach the market. Many of these drugs are likely to fail during clinical trials. The field is evolving quickly and some experts believe that the current therapies are only the beginning of an exciting renaissance for drug discovery in weight management and other applications.

Raymond Stevens is the chief executive at Structure Therapeutics. The company works on GLP-1s that are taken orally. We're still learning a lot about how to dose the drugs, and how much weight loss certain people should have. It's still early days.

Stevens says that oral drugs can be used to titrate, or increase the dose, over time without causing as many side effects on the gastrointestinal tract as injectable versions.

Hsueh of the Ohio State University noted that 5-10% of patients cannot tolerate nausea, vomiting, and other side-effects that can be caused by the drugs currently available.

She said that the insurance coverage of the drugs is the first area where she believes improvements can be made. She claims that many insurance companies consider weight loss cosmetic, and will not cover the drugs which cost more than $1,000 a month.

Aronne believes that a clinical trial, which is expected to be completed this summer, could change the situation if it's successful. Novo Nordisk tests whether Wegovy reduces the risk of stroke and heart disease in overweight or obese people without type 2 diabetes. Semaglutide already has a protective effect.

Aronne stated that it was a very exciting moment to be at this stage.