Are These New Weight Loss Drugs Potential Game Changers?

The field of obesity and diabetes medicine is evolving fast during the GLP-1 era as scientists work to develop new drugs. Scientists shared the latest research this week at the annual meeting of the European Association for the Study of Diabetes.

Results from a late-stage (phase 3) trial of retatrutide generated buzz because the once-a-week injectable medication triggered massive weight loss. This so-called “Godzilla” drug is expected to become a blockbuster should it receive FDA approval next year.

But results for other promising drugs in earlier, phase 2 trials also got scientists talking. The findings hint there’s even more change to come with medication-assisted weight loss.

“There are many companies that have some [weight loss] molecule they’re looking at,” says Christine Gallagher, the associate director for research and policy for the STOP Obesity Alliance at George Washington University’s Milken Institute School of Public Health in Washington, DC. “This is not a field that is going away.”

Here are three medications to watch for.

EloraTZP Amps Up the Power of Tirzepatide

EloraTZP is an experimental medication from Eli Lilly, the creators of the tirzepatide drugs Zepbound and Mounjaro as well as the Foundayo pill (orforglipron).

Tirzepatide and eloralintide work together to regulate blood sugar, control appetite, and slow digestion, driving weight loss results that in a phase 2 clinical trial rivaled those of retatrutide.

In the trial, which included almost 400 adults with obesity or overweight and type 2 diabetes, those who took EloraTZP lost up to an average of 54.1 pounds (lb) or 23.3 percent of their body weight.

In comparison, those who took a 15 mg dose of tirzepatide alone lost an average of 34.4 lb or 14.8 percent of their body weight.

EloraTZP users experienced mostly gastrointestinal side effects, which led to up to 27 percent of them stopping the medication. Still, “the weight loss and side effects are comparable with other second-generation anti-obesity medications,” says Richard Siegel, MD, a codirector of the Diabetes and Lipid Center at Tufts Medical Center and an endocrinologist at Tufts Medicine Weight & Wellness Center in Stoneham, Massachusetts.

Side effects as well as weight loss may increase as medications target more hormone receptors. “That can potentially come with more side effects,” says Mir Ali, MD, the medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California.

Trevogrumab Aims to Minimize Muscle Loss

Trevogrumab isn’t a weight loss medication per se, but it’s designed to be given alongside semaglutide (the active ingredient in Wegovy and Ozempic) to minimize muscle loss, a common concern with weight loss medications.

In the first part of the trial, those who took semaglutide lost 6.7 percent of their lean muscle mass over 26 weeks. But participants who took semaglutide and 75 mg of trevogrumab lost only 3.3 percent of ⁠their muscle mass.

“Muscle loss is always a concern in any kind of weight loss process,” Dr. Ali says. “Anything that can help to reduce muscle loss is going to be an improvement.” Not only can muscle preserve strength, but more muscle burns more calories at rest, he points out.

On the other hand, Dr. Siegel notes, it’s not yet clear if less muscle mass loss translates to more strength and mobility in patients.

CBL-514 Kills Fat Cells to Prevent Weight Regain

Many weight loss medications target specific hormone receptors in the body to reduce hunger and slow digestion. But CBL-514 takes a novel approach by killing fat cells, a process known as apoptosis of adipocytes, with the goal of making it easier for people who’ve lost weight to keep it off.

While medications like semaglutide and tirzepatide can help people lose weight, they don’t target fat alone, Ali points out.

CBL-514 reduced the layer of fat just below the skin (known as subcutaneous adipose tissue) by 150 milliliters (mL) in nearly 70 percent of participants by the eight-week follow-up. By comparison, none of those who received the placebo reached this marker.

What Doctors Have to Say About New Weight Loss Drugs in Development

As more weight loss drugs make their way through the research pipeline and become available, doctors are hoping that patients will benefit from lower costs and greater choice.

“More options should help to reduce prices for medication, which would ideally increase access through more insurance plans,” says Siegel.

Additional medications also allow providers to better tailor treatment to the patient, according to Ali. “No single medication is effective for everybody,” he says. “Having different options available is important.”