The next wave of obesity drugs is coming soon.
Pharmaceutical companies are racing to develop GLP-1 drugs following the breakout success of Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound.
Some of the experimental drugs could go beyond diabetes and weight loss, improving liver and heart function. while reducing side effects such as muscle loss common with 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 see many, many different drug candidates in development, from very early preclinical stages to late clinical stages,” Dr. Marlon said. Pragnell, ADA vice president of research and science. “It’s very exciting to see so much happening right now.”
Much of the data presented comes from animal studies or early human trials. However, some presentations include intermediate or late-stage trials, according to a list shared by the organization.
Approval from the Food and Drug Administration will likely take years for most. Some of the drugs presented may become available by prescription in the United States in the coming years.
“We have seen an unprecedented acceleration in GLP drug development,” said Dr. Christopher McGowan, a gastroenterologist who runs a weight-loss clinic in Cary, North Carolina. “We are now firmly entrenched in the GLP era. »
Although existing medications are highly effective, new medications that are more affordable and have fewer side effects are needed, McGowan added.
It’s not just GLP-1 drugs in the pipeline. On Thursday, ahead of the diabetes conference, Danish biotech company Zealand Pharma released data showing that a high dose of its experimental weight loss drug petrelintide helped reduce body weight by 8.6%. on average at 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 like nausea typically associated with GLP-1 drugs such as Wegovy and Zepbound.
Can the glucagon hormone help with weight loss?
GLP-1 drugs work, in part, by slowing down how quickly food passes through the stomach, causing people to feel full longer. In many of the upcoming weight loss drugs, another 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 presented at Sunday’s conference is called pemvidutide, from the Maryland-based biotechnology company Altimmune.
The drug contains the hormone GLP-1, a key ingredient in Ozempic and Wegovy, in addition to glucagon.
Altimmune released data from a phase 2 trial involving 391 obese or overweight adults with at least one weight-related comorbidity such as high blood pressure. Patients were randomized to receive either one of three doses of pemvidutide or a placebo for 48 weeks.
The researchers found that patients who received the highest dose of the drug lost an average of 15.6% of their body weight after 48 weeks, compared to a 2.2% body weight loss seen in patients who received a placebo. In similar trials, semaglutide was shown to reduce body weight by approximately 15% after 68 weeks.
These are not direct comparisons because the drugs were not compared in a comparative clinical trial.
Dr. Scott Harris, Altimmune’s chief medical officer, said the drug has been shown to help people lose weight and has benefits for liver and heart health. Additionally, the drug has shown benefits in preserving lean mass. Some studies have suggested that semaglutide, the active ingredient in Ozempic and Wegovy, may cause muscle loss.
“If people take medication 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 people who received pemvidutide lost an average of 21% of their lean mass, which is less than the about 25% of lean mass that people typically lose with diet and exercise.
“We are the next wave of obesity drugs,” said Vipin Garg, president and CEO of Altimmune. “The first wave of mechanisms were entirely driven by appetite suppression. We add another component.
Altimmune plans to begin a phase 3 trial soon. The company hopes the drug will be available in the United States in 2028.
Competition could bring down costs
Experts say it’s important to increase the number of weight loss medications available for several reasons.
More options could also help ease shortages seen in the United States with weight-loss drugs from Novo Nordisk and Lilly.
Latest news on weight loss drugs
Increased competition could bring down high drug costs over time. A monthly supply of Wegovy or Zepbound can cost more than $1,000, experts say, which is often financially untenable for many patients.
Patients may also respond differently to treatments, said Dr. Fatima Cody Stanford, associate professor of medicine and pediatrics at Harvard Medical School. In fact, some have found existing GLP-1 options ineffective.
“Different GLP-1 drugs may have different levels of effectiveness and potency,” she said. “Some patients may respond better to one medication 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, but I never saw it,” said the 38-year-old from Elida, New Mexico. Griffin weighed about 300 pounds and only lost about 10 pounds in two years. She said her “expectations were pretty much shattered because of this.”
Amid battles and insurance 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 me, for someone for whom medication isn’t working.”
The prospect of new drugs on the horizon excites Griffin. “I would be willing to try it,” she said, adding that “it could change my life, honestly, and you know that alone gives me something to look forward to.”
Other drugs in preparation
Eli Lilly, which makes Zepbound and the diabetes version Mounjaro, has two other GLP-1 drugs in development.
On Sunday, Lilly released new data on retatrutide, an injectable drug that combines GLP-1 and glucagon, as well as another hormone called GIP. GIP is thought to improve the way the body breaks down sugar.
In an earlier trial, retatrutide helped people lose an average of about 24 percent of their body weight, or the equivalent of about 58 pounds—more weight loss than any other drug on the market.
New findings showed that weekly treatment also significantly reduced blood sugar levels in people with type 2 diabetes.
On Saturday, new discoveries were also made about experimental mazdutide, which Lilly is developing in partnership with Chinese biotechnology company Innovent Biologics. The drug combines GLP-1 and glucagon.
In a phase 3 study in China of overweight or obese adults, researchers found that after 48 weeks, a 6-milligram dose of the drug resulted in an average reduction in body weight of 14.4 percent.
The drug also led to a reduction in serum uric acid – a chemical that can build up in the blood, causing health problems, and which has been linked to obesity, according to Dr Linong Ji, director of the Peking University Diabetes Center, which presented the results.
This was “very 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.
Improve metabolic conditions
An estimated 75% of obese people have nonalcoholic fatty liver disease and 34% have MASH, or steatohepatitis associated with metabolic dysfunction, according to researchers at German drugmaker Boehringer Ingelheim. Fatty liver disease occurs when the body begins to store fat in the liver. This can progress to MASH, when fat accumulation causes inflammation and scarring.
In a phase 2 trial in people who were overweight or obese, Boehringer Ingelheim’s survodutide, which uses both GLP-1 and glucagon, resulted in 19% weight loss 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 for people with cardiovascular, renal and metabolic diseases,” said Dr. Waheed Jamal, Boehringer Ingelheim vice president and head of cardiometabolic medicine.
On Friday, the company released 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 obesity, found that the drug helped improve blood sugar levels.
The company plans to launch a phase 3 trial.