The next wave of obesity drugs is coming soon.
Drug companies are racing to develop GLP-1 drugs following the blockbuster success of Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound.
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Some of the experimental drugs may go beyond diabetes and weight loss, improving liver and heart function while reducing side effects such as muscle loss common to the existing medications. At the 2024 American Diabetes Association conference in Orlando, Florida, researchers are expected to present data on 27 GLP-1 drugs in development.
“We’ve heard about Ozempic and Mounjaro and so on, but now we’re seeing lots and lots of different drug candidates in the pipeline, from very early-stage preclinical all the way through late-stage clinical,” said Dr. Marlon Pragnell, ADA’s vice president of research and science. “It’s very exciting to see so much right now.”
A large portion of the data presented comes from animal studies or early-stage human trials. However, some presentations include mid-to late-stage trials, according to a list shared by the organization.
Approval by the Food and Drug Administration is likely years away for most. Some of the drugs showcased could be available for prescription in the U.S. within the next few years.
“We’ve witnessed an unprecedented acceleration in the development of GLP drugs,” said Dr. Christopher McGowan, a gastroenterologist who runs a weight loss clinic in Cary, North Carolina. “We are now firmly entrenched in the era of the GLP.”
Health
While the existing drugs are highly effective, new drugs that are more affordable and have fewer side effects are needed, McGowan added.
There aren’t just GLP-1 drugs in the pipeline. On Thursday, ahead of the diabetes conference, Denmark-based biotech firm Zealand Pharma released data that showed a high dose of its experimental weight loss drug petrelintide helped reduce body weight by an average of 8.6% at 16 weeks.
The weekly injectable medication is unique because it mimics the hormone amylin, which helps control blood sugar. The hope is patients will experience fewer side effects like nausea commonly associated with GLP-1 drugs such as Wegovy and Zepbound.
Can glucagon hormone help with weight loss?
GLP-1 medications work, in part, by slowing down how quickly food passes through the stomach, leading people to feel fuller longer. In several of the upcoming weight loss drugs, a different hormone called glucagon is in the spotlight. Glucagon is a key blood-sugar-regulating hormone that can mimic the effects of exercise.
One of the drugs featured at the conference on Sunday is called pemvidutide, from Maryland-based biotech firm Altimmune.
The drug contains the GLP-1 hormone, a key ingredient in Ozempic and Wegovy, in addition to glucagon.
Altimmune released data from a phase 2 trial of 391 adults with obesity or who are overweight with at least one weight-related comorbidity such as high blood pressure. Patients were randomized to either get one of three doses of pemvidutide or a placebo for 48 weeks.
Researchers found that patients who got the highest dose of the drug lost on average 15.6% of their body weight after 48 weeks, compared to the 2.2% body weight loss seen in patients who got a placebo. In similar trials, semaglutide was shown to reduce body weight by around 15% after 68 weeks.
These are not direct comparisons because the drugs weren’t compared in a head-to-head clinical trial.
Dr. Scott Harris, Altimmune’s chief medical officer, said the drug has been shown to help people lose weight, as well as provide health benefits to the liver and heart. What’s more, the drug has shown benefits in preserving lean body mass. Some studies have suggested that semaglutide, the active ingredient in Ozempic and Wegovy, can cause muscle loss.
“If people take the drugs long term, what’s going to be their long-term health? What’s going to be the long-term effects on their body composition, their muscle, their ability to function?” he said.
Harris said that people who got pemvidutide lost on average 21% of their lean body mass, which is lower than the around 25% of lean body mass people typically lose with diet and exercise.
“We’re the next wave of obesity drugs,” Altimmune President and CEO Vipin Garg said. “The first wave of mechanisms was all driven by appetite suppression. We are adding another component.”
Altimmune expects to begin a phase 3 trial soon. The company hopes the drug will be available in the U.S. sometime in 2028.
Competition could drive down costs
Expanding the number of weight loss drugs available is important for several reasons, experts say.
More options could also help alleviate the shortages seen in the U.S. with Novo Nordisk’s and Lilly’s weight loss drugs.
Increased competition could drive down the high cost of the drugs over time. A month’s supply of Wegovy or Zepbound can cost more than $1,000, often financially untenable for many patients, experts say.
Patients can also respond differently to treatments, said Dr. Fatima Cody Stanford, an associate professor of medicine and pediatrics at Harvard Medical School. In fact, some have found the existing GLP-1 options ineffective.
“Different GLP-1 drugs may have varying levels of efficacy and potency,” she said. “Some patients may respond better to one drug over another, depending on how their body metabolizes and responds to the medication.”
Since starting Ozempic in June 2022, Danielle Griffin has not seen the results her doctor predicted. “She really expected to see a huge difference in my weight, and I just never saw it,” said the 38-year-old from Elida, New Mexico. Griffin weighed about 300 pounds and has lost only about 10 pound in two years. She said her “expectations were pretty much shattered from that.”
Amid insurance battles and shortages, she has also tried Wegovy and Mounjaro, but didn’t see a difference in her weight.
“I don’t feel like there are options, especially for myself, for someone who the medications not working for.”
The prospect of new medications on the horizon excites Griffin. “I would be willing to try it,” she said, adding that “it could be life changing, honestly, and you know that alone gives me something to look forward to.”
More drugs in the pipeline
Eli Lilly, which makes Zepbound and the diabetes version Mounjaro, has two more GLP-1 drugs in development.
On Sunday, Lilly released new data about retatrutide, an injectable drug that combines GLP-1 and glucagon, plus another hormone called GIP. GIP is thought to improve how the body breaks down sugar.
In an earlier trial, retatrutide helped people lose, on average, about 24% of their body weight, the equivalent of about 58 pounds — greater weight loss than any other drug on the market.
New findings showed the weekly medication also significantly reduced blood sugar levels in people with Type 2 diabetes.
On Saturday, there were also new findings on the experimental mazdutide, which Lilly is developing in partnership with the Chinese biotech firm Innovent Biologics. The drug combines GLP-1 and glucagon.
In a phase 3 study of adults in China who were overweight or had obesity, researchers found that after 48 weeks, a 6-milligram dose of the drug led to an average body weight reduction of 14.4%.
The drug also led to a reduction in serum uric acid — a chemical that can build up in the bloodstream, causing health problems, and has been associated with obesity, according to Dr. Linong Ji, director of the Peking University Diabetes Center, who presented the findings.
That was “quite unique and never reported for other GLP-1-based therapies,” he said in an interview.
The drug could be approved in China in 2025, Ji said.
Improving metabolic conditions
An estimated 75% of people with obesity have nonalcoholic fatty liver disease and 34% have MASH, or metabolic dysfunction-associated steatohepatitis, according to researchers with the German drugmaker Boehringer Ingelheim. Fatty liver disease occurs when the body begins to store fat in the liver. It can progress to MASH, when fat buildup causes inflammation and scarring.
In a phase 2 trial of people who were overweight or had obesity, Boehringer Ingelheim’s survodutide, which uses both GLP-1 and glucagon, led to weight loss of 19% at 46 weeks. Another phase 2 study in people with MASH and fibrosis found that 83% of participants also showed improvement in MASH.
Survodutide “has significant potential to make a meaningful difference to people living with cardiovascular, renal and metabolic conditions,” said Dr. Waheed Jamal, Boehringer Ingelheim’s corporate vice president and head of cardiometabolic medicine.
On Friday, the company released two studies on the drug. One, in hamsters, found that weight loss was associated with improvements in insulin and cholesterol. The second, in people with Type 2 diabetes or people with obesity, found the drug helped improve blood sugar levels.
The company is looking to begin a phase 3 trial.
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