New GLP-1 Drugs Promise Weight Loss, Health Benefits

The next wave of obesity drugs is coming soon.

Pharmaceutical companies are racing to develop GLP-1 Medicines following the box office 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 to improving liver and heart function while reducing side effects such as muscle loss common to 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 the preclinical stage to the late clinical stage,” said Dr. Pragnell, vice president of research and ADA science. “It’s very exciting to see so much now.”

Much of the data presented comes from animal studies or early-stage human trials. However, some presentations include mid- to late-stage testing, according to a list shared by the organization.

Food and Drug Administration approval will likely take years for most. Some of the medicines presented may be available for prescription in the US in the coming years.

“We have witnessed 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 rooted in the LPG era.”

While existing medications are highly effective, new medications are needed that are more affordable and have fewer side effects, McGowan added.

There are not just GLP-1 drugs in development. On Thursday, ahead of the diabetes conference, Denmark-based biotechnology company Zealand Pharma released data that showed a high dose of its experimental drug weight loss drug petrelintide helped reduce body weight by an average of 8.6% in 16 weeks.

The weekly injectable medication is unique because it mimics the hormone amylin, which helps control blood sugar. The hope is that patients will experience fewer side effects such as nausea commonly associated with GLP-1 medications such as Wegovy and Zepbound.

Can the hormone glucagon help with weight loss?

GLP-1 medications work, in part, by slowing down how quickly food passes through the stomach, making people feel fuller for longer. In several of the upcoming weight loss medications, a different hormone called glucagon is featured. Glucagon is a blood sugar-regulating hormone that can mimic the effects of exercise.

One of the drugs presented at Sunday’s conference is called pemviductide, from Maryland-based biotechnology company Altimmune.

The medicine contains the hormone GLP-1, a key ingredient in Ozempic and Wegovy, in addition to glucagon.

Altimmune released data from a phase 2 study of 391 adults who were obese or overweight and had at least one weight-related comorbidity, such as hypertension. Patients were randomized to receive one of three doses of pemviductide 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 the 2.2% body weight loss seen in patients who received a placebo. In similar trials, semaglutide has been shown to reduce body weight by around 15% after 68 weeks.

These are not direct comparisons because the drugs were not 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 liver and heart health benefits. Furthermore, the medication has demonstrated benefits in preserving lean body mass. Some studies suggested that semaglutide, the active ingredient in Ozempic and Wegovy, can cause muscle loss.

“If people take the medications long-term, what will their long-term health be? What will be the long-term effects on body composition, muscles and ability to function?” he said.

Harris said people who took pemviductide lost an average of 21% of their lean body mass, which is less than the roughly 25% of lean body mass that people typically lose through diet and exercise.

“We are the next wave of obesity medicines,” said Altimmune President and CEO Vipin Garg. “The first wave of mechanisms were all driven by appetite suppression. We are adding another component.”

Altimmune hopes to begin a phase 3 trial soon. The company expects the drug to be available in the US in 2028.

Competition can reduce costs

Expanding the number of weight-loss medications available is important for several reasons, experts say.

More options could also help alleviate shortages seen in the U.S. with weight-loss drugs from Novo Nordisk and Lilly.

Increased competition could reduce the high cost of medicines over time. A month’s supply of Wegovy or Zepbound can cost more than $1,000, 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. In fact, some have found existing GLP-1 options to be ineffective.

“Different GLP-1 medications can have varying 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 predicted by her doctor. “She really expected to see a big 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 destroyed by 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 medications don’t work.”

The prospect of new medicines on the horizon excites Griffin. “I would be willing to try,” she said, adding that “it could change my life, honestly, and you know that alone gives me something to look forward to.”

More medicines 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 on retatrutide, an injectable medication that combines GLP-1 and glucagon, as well as another hormone called GIP. GIP is believed to improve the way the body breaks down sugar.

In a previous trial, retatrutide helped people lose, on average, around 24% of their body weight, the equivalent of around 23 kilograms – greater weight loss than any other medicine on the market.

New findings showed that weekly medication also significantly reduced blood sugar levels in people with type 2 diabetes.

On Saturday, there were also new discoveries in the experiment mazdutide, which Lilly is developing in partnership with Chinese biotechnology company Innovative biological products. The drug combines GLP-1 and glucagon.

In a phase 3 study of adults in China who were overweight or obese, researchers found that after 48 weeks, a 6-milligram dose of the drug led to an average reduction in body weight 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 linked to obesity, according to Dr. Linong Ji, director of the Diabetes Center at Peking University, which presented the evidence.

This 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.

Improve metabolic conditions

An estimated 75% of people with obesity have non-alcoholic fatty liver disease and 34% have MASH, or steatohepatitis associated with metabolic dysfunction, according to researchers at German pharmaceutical company Boehringer Ingelheim. Fatty liver disease occurs when the body begins to store fat in the liver. It can progress to MASH, when fat accumulation causes inflammation and scarring.

In a phase 2 trial in people who are overweight or obese, Boehringer Ingelheim’s survodutide, which uses both GLP-1 and glucagon, led to 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 living with cardiovascular, kidney and metabolic problems,” said Dr. Waheed Jamal, Boehringer Ingelheim 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 obesity, found that the drug helped improve blood sugar levels.

The company intends to begin a phase 3 trial.