The next wave of obesity drugs is coming.
Pharmaceutical companies are rushing to develop GLP-1 drugs after the great success of Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound.
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 that occur with existing drugs. 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 a lot of different drug candidates in the pipeline, from very early preclinical stages all the way to late clinical stages,” said Dr. Marlon. Pragnell, ADA’s vice president of research and science. “It’s very exciting to see so much now.”
Much of the data presented comes from animal studies or early human trials. However, according to a list shared by the organization, some presentations will include mid- to late-stage trials.
Approval from the Food and Drug Administration will likely take years for most. Some of the medications presented may become available by prescription in the US in the coming years.
“We have witnessed an unprecedented acceleration in the development of GLP drugs,” says Dr. Christopher McGowan, a gastroenterologist who runs a weight-loss clinic in Cary, North Carolina. “We are now firmly entrenched in the GLP era.”
While existing drugs are highly effective, new drugs are needed that are more affordable and have fewer side effects, McGowan added.
It’s not just GLP-1 drugs in the pipeline. On Thursday, ahead of the diabetes conference, Denmark-based biotechnology company Zealand Pharma released data showing that a high dose of its experimental weight-loss drug petrelintide helped reduce body weight by an average of 8.6% after 16 weeks.
The weekly injectable medication is unique because it mimics the hormone amylin, which helps control blood sugar levels. The hope is that patients will experience fewer side effects, such as nausea that often accompanies GLP-1 drugs such as Wegovy and Zepbound.
Can glucagon hormone help with weight loss?
GLP-1 drugs work in part by slowing the speed at which food passes through the stomach, helping people feel full longer. In several of the emerging weight loss medications, another hormone called glucagon is in the spotlight. Glucagon is an important blood sugar-regulating hormone that can mimic the effects of exercise.
One of the drugs presented at the conference on Sunday is called pemvidutide, from Maryland-based biotech company Altimmune.
In addition to glucagon, the drug contains the GLP-1 hormone, a key ingredient in Ozempic and Wegovy.
Altimmune released data from a Phase 2 study of 391 adults with obesity or overweight and at least one weight-related comorbidity, such as high blood pressure. Patients were randomized to receive one of three doses of pemvidutide or a placebo for 48 weeks.
Researchers found that patients given the highest dose of the drug lost an average of 15.6% of their body weight after 48 weeks, compared to the 2.2% weight loss in patients given a placebo. In similar studies, semaglutide was shown to reduce body weight by approximately 15% after 68 weeks.
These are not direct comparisons because the drugs have not been compared in a head-to-head clinical trial.
Dr. Scott Harris, chief medical officer of Altimmune, said the drug has been shown to help people lose weight and provide health benefits for the liver and heart. Additionally, the drug has shown benefits in maintaining lean body mass. Some research has suggested that semaglutide, the active ingredient in Ozempic and Wegovy, may cause muscle loss.
“If people take the drugs long term, what will their long-term health be like? What will be the long-term effects on their body composition, their muscles, their ability to function?” he said.
Harris said that people given pemvidutide lost an average of 21% of their lean mass, which is lower than the approximately 25% of lean mass that people typically lose with diet and exercise.
“We are the next wave of anti-obesity medicine,” said Vipin Garg, president and CEO of Altimmune. “The first wave of mechanisms were 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 US sometime in 2028.
Competition could drive down costs
Expanding the number of weight loss medications available is important for several reasons, experts say.
More options could also help alleviate U.S. shortages of Novo Nordisk and Lilly’s weight-loss drugs.
Increased competition could reduce the high cost of the drugs over time. A month’s supply of Wegovy or Zepbound can cost more than a thousand dollars, which is often financially unsustainable for many patients, experts say.
Patients may also respond differently to treatments, said Dr. Fatima Cody Stanford, associate professor of medicine and pediatrics at Harvard Medical School. Some even find that existing GLP-1 options are ineffective.
“Different GLP-1 drugs may have different levels of efficacy and potency,” she said. “Some patients may respond better to one medication than 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 a huge difference in my weight, but I just never saw it,” said the 38-year-old from Elida, New Mexico. Griffin weighed about 300 pounds and has only lost about 10 pounds in two years. She said her “expectations were pretty much shattered as a result.”
Amid insurance issues and shortages, she also tried Wegovy and Mounjaro, but saw no difference in her weight.
“I don’t feel like there are any options, especially for myself, for someone whose medications aren’t working.”
The prospect of new drugs on the horizon excites Griffin. “I’d like to try it,” she said, adding that “it could change my life, honestly, and you know that just gives me something to look forward to.”
There are more drugs in the pipeline
Eli Lilly, which makes Zepbound and its diabetes version Mounjaro, has two more GLP-1 drugs in development.
On Sunday, Lilly published new data on retatrutide, an injectable drug that combines GLP-1 and glucagon, plus another hormone called GIP. GIP is thought to improve the way the body breaks down sugar.
In a previous study, retatrutide helped people lose an average of about 24% of their body weight, the equivalent of about 28 pounds – a greater weight loss than any other drug on the market.
New findings showed that the weekly medication also significantly lowered blood sugar levels in people with type 2 diabetes.
Saturday there were also new findings about the experimental mazdutide, which Lilly is developing in collaboration with the Chinese biotech company Innovent Biologics. The drug combines GLP-1 and glucagon.
In a Phase 3 study of overweight or obese adults in China, researchers found that a 6-milligram dose of the drug led to an average 14.4% reduction in body weight after 48 weeks.
The drug also led to a reduction in serum uric acid – a chemical that can build up in the bloodstream, cause health problems and has been linked to obesity, said Dr. Linong Ji, director of the Beijing 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.
Improvement of metabolic conditions
According to researchers at German drugmaker Boehringer Ingelheim, an estimated 75% of obese people have non-alcoholic fatty liver disease and 34% have MASH, or metabolic dysfunction-associated steatohepatitis. Fatty liver disease occurs when the body begins to store fat in the liver. It can develop into MASH, when the fat deposits cause inflammation and scarring.
In a phase 2 trial in overweight or obese people, Boehringer Ingelheim’s survodutide, which uses both GLP-1 and glucagon, led to a 19% weight loss after 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 for people living with cardiovascular, renal and metabolic conditions,” said Dr. Waheed Jamal, vice president of Boehringer Ingelheim and head of cardiometabolic medicine.
On Friday, the company published two studies on the drug. One study in hamsters found that weight loss was associated with improvements in insulin and cholesterol. The second, in people with type 2 diabetes or those who are obese, found that the drug helped improve blood sugar levels.
The company wants to start a phase 3 trial.
This article was originally published on NBCNews.com