The new crop of drugs on the market for type 2 diabetes and obesity, including popular drugs such as Ozempic and Wegovy, are more effective than previous drugs for weight loss, but doctors and researchers say there is still room for improvement.

Next-generation alternatives now in development may be lighter and more convenient to carry, turbo-charged and offer weight loss and additional health benefits.

“This is all very good news,” said Dr. Louis Aron, director of the Center for Comprehensive Weight Management at Weill Cornell Medicine. “We need drugs that work in different ways.”

Some of the more advanced experimental drugs are drugs that are taken in pill form rather than as an injection. Ozympic and Munjaro, currently approved for type 2 diabetes, and Wegovi, which is cleared for weight loss, are all given once a week by self-injection.

Novo Nordisk, which makes Ozympic and Wegovin, has a daily tablet version of the same called semaglutide, which is approved for diabetes and is testing higher doses for weight loss. In the last stage Study results The drug, released this week, helped people lose 15% of their body weight over 68 weeks, compared to 2.4% for people who took a placebo.

Novo Nordisk said the results, which were not published in a peer-reviewed journal, were similar to the weight loss seen with the injectable Wegovy. The side effects were the same, the company said; Gastrointestinal issues such as nausea and diarrhea are more common with this class of drugs known as GLP-1 analogues. “Most were mild to moderate and decreased over time,” Novo Nordisk said.

The company plans to seek regulatory approval in the US and Europe this year, and availability will depend on how the drugs are prioritized. and on production capacity; Because demand exceeds supply, Wegovi is currently being distributed to some patients.

But, even though it comes in tablet form, oral semaglutide – sold under the brand name Rybelsus for type 2 diabetes – can still be complicated to take, doctors say.

“Patients taking Rybelsus should be instructed on strict requirements before and after oral administration,” said Dr. Priya Jaisingani, an endocrinologist and obesity medicine specialist at NYU Langone Health. You can’t eat, drink or take any other medicine within 30 minutes of taking the medicine, she said, or the effect may be reduced.

Other oral GLP-1 drugs are in development that can be taken with food, including two from Pfizer. The company published Data A study published this week in the journal JAMA Network published a study on a twice-daily pill called danuglipron for people with type 2 diabetes. The mid-stage trial showed the drug reduced blood sugar and led to significant weight loss over 16 weeks, compared with other drugs in the class, researchers said. The side effects were the same.

Pfizer has a second experimental drug in development, lotiliprone, which is designed to be taken orally once a day. The company plans to select one of the drugs to enter late-stage clinical trials in diabetes and obesity, which are expected to begin next year.

About two dozen other experimental drugs are in development, designed to be taken as pills for obesity and related conditions, according to research by financier TD Cowen.

“Of course, a pill would be more attractive to most people,” said Dr. Willa Hsueh, director of the Diabetes and Metabolism Research Center at The Ohio State University Wexner Medical Center. In addition to avoiding needles, it may be better if people stop taking the drug because of side effects because they don’t last as long, he said. Once people reach a certain point of weight loss on injectable drugs, a pill can be useful for weight maintenance, she said.

But Hsu said, “Some patients prefer an injection once a week to a pill if they have to take a handful of pills every day.”

There is also no shortage of injectable drugs in development, with many trying to outdo the weight loss options available today.

Eli Lilly’s tirzepatide, approved as Mounjaro for type 2 diabetes, led to a 21 percent weight loss in a 72-week high-dose study. Results It was published in the New England Journal of Medicine last year.

The drug is expected to receive FDA approval for weight loss in diabetics this year or early 2024. In addition to GLP-1, it builds on the 15% weight loss shown for Wegovy by adding a target called GIP.

“Semaglutide has a GLP-1 effect and tirzepatide has two effects, GIP and GLP-1 – so it has more weight loss – [in] The next generation of drugs, some will have triple effects,” said Weill Cornell’s Aaron.

One such drug, also in development at Lilly, targets a target called glucagon in addition to GIP and GLP-1. Aaron, who has served as a primary investigator on obesity clinical trials and has consulted for companies developing weight-loss drugs, calls it “Triple G.”

“This seems to go beyond the 25% weight loss,” Aaron said.

Lilly said it expects to begin late-stage trials of a drug called retatrutide this year.

If successful, it could be compared to a combination drug from Novo Nordisk called Cagrisema, a combination of semaglutide and cagrilintide, a drug that works by stimulating the hormone amylin to promote weight loss.

“We will have more treatments that are more effective,” Aaron said.

Other drugs still in development aim to improve the breakdown of fat in the liver, which could help conditions such as nonalcoholic steatohepatitis, which Aaron says is a leading cause of liver failure and the need for a transplant. Another experimental drug targets a receptor in the muscle that causes weight loss to prevent overall weight loss.

Many of these drugs may be years before they reach the market. Some may fail in clinical trials. But the field is moving fast, and some experts see weight management and related applications as just the beginning of a revolution in drug discovery.

“We’re in the early stages of the race,” says Raymond Stevens, CEO of the biotech company. Structure therapeuticsActing on oral GLP-1s. “We’re still learning a lot about how to precisely prescribe the drugs, how much weight certain individuals need to lose. So these are the first days.

Stevens said oral medications may offer an option to titrate, or increase the dose over time, without causing the same gastrointestinal side effects that people may have with the injectable versions.

Hsueh of Ohio State University noted that 5% to 10% of patients may experience nausea, vomiting and other side effects from current medications.

But the first thing she said needs to be improved around the drugs is their insurance coverage. Many insurers consider weight loss to be cosmetic and refuse to cover drugs that cost more than $1,000 a month.

That could change if the clinical trial, which is expected to have results this summer, is successful, Aaron said. Novo Nordisk is investigating whether Wegovi can help reduce the risk of heart disease and stroke in people who are obese or do not have type 2 diabetes – semaglutide has already shown a protective effect.

As Aaron said, I think it’s very important to test the extent to which these drugs have a preventive health effect, and it’s exciting that we’re at this stage.

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