This content originally appeared on Everyday Health. Republished with permission.

By Ross Wollen

Key Takeaways

In clinical trials, the drug pemvidutide helped subjects drop more than 15 percent of their body weight, with less muscle loss than rival GLP-1 drugs.
Pemvidutide also reduced cholesterol, but did not affect blood sugar levels.
The medication will progress to late-stage trials, the last step before its maker seeks FDA approval.

A medication now in clinical trials is sparking interest because it can cause significant weight loss while minimizing loss of lean muscle — something its competitors don’t do quite as well. Researchers shared results from a phase 2 trial this week at the American Diabetes Association’s annual scientific conference.

Pemvidutide, manufactured by a company called Altimmune, belongs to a category of weight loss medication that includes semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). These drugs mimic the activity of a hormone called GLP-1 (glucagon-like peptide 1) that is released in the gut after eating. By stimulating insulin production and triggering feelings of satiety in the brain, GLP-1 medications lower blood sugar levels and curb appetite.

Unlike other GLP-1 drugs, pemvidutide also mimics the hormone glucagon, which instructs the liver to release stored sugar into the bloodstream.

How Well Does Pemvidutide Work?

The trial evaluated pemvidutide’s effectiveness in more than 200 adults without diabetes who were overweight or had obesity. After 48 weeks of treatment, subjects at the highest dose of pemvidutide lost an average of 15.6 percent of their body weight, and appeared to still be losing weight even as the research wrapped up. They also saw significant reductions in blood lipid levels, including triglycerides and total cholesterol.

Participants experienced no changes in fasting blood sugar or A1C. That makes pemvidutide different from semaglutide and tirzepatide, which were originally developed to treat type 2 diabetes.

“It’s the glucagon component,” explained Louis Aronne, MD, at the conference; he is a professor at Weill Cornell Medicine in New York City and the trial’s principal investigator. “Glucagon, by making the liver make glucose, raises blood sugar. The GLP-1 reduces sugar.” The two hormones appear to cancel each other out.

Dr. Aronne noted that pemvidutide “may have important effects on the quality of weight loss,” as well as on the many health risks associated with obesity.

Pemvidutide Helps Preserve Muscle During Weight Loss

All weight loss involves sacrificing some lean mass, mainly muscle. But some experts have raised alarms that semaglutide and other drugs in the GLP-1 class are causing too much muscle loss, which could impair a person’s ability to function in daily life or even (in a worst-case scenario) lead to serious frailty.

“As the focus shifts to long-term weight management, the preservation of lean mass will be critical for patient care,” Aronne said.

There is only a small amount of data on the body composition of participants in significant GLP-1 trials, but that evidence has raised some red flags. Two small analyses, for example, found about that about 40 percent of weight loss on semaglutide came from the loss of lean mass.[1][2] Aronne stated that conventional weight loss interventions typically incur about 25 percent loss from lean mass.

The pemvidutide trial, by contrast, found that only 21.9 percent of weight loss came from lean mass. Aronne said that researchers did not yet understand why pemvidutide has this unique effect on body composition.

Obesity experts are still debating about these claims of excessive muscle loss, with some saying that the concern is not supported by data.[3] But GLP-1 manufacturers appear to be taking the issue very seriously, and are investing heavily in treatments that could limit the loss of lean mass.[4]

In the meantime, doctors and nutritionists widely recommend that people using weight loss drugs take care to exercise and consume enough protein, both of which may help preserve muscle.

Pemvidutide Might Help Treat Liver Disease

In addition to obesity, pemvidutide may also one day be used to treat metabolic dysfunction–associated steatohepatitis, a liver condition known as MASLD. The disease, which is usually asymptomatic, is defined by a high concentration of fat within the liver (it was previously called nonalcoholic fatty liver disease, or NAFLD).

In some patients with MASLD, the liver’s accumulation of fat will progress to a severe and dangerous state named MASH. Additional trials are planned to address pemvidutide’s ability to treat liver disease.

What Are the Side Effects of Pemvidutide?

As with other GLP-1 drugs, people in the pemvidutide trial experienced a high rate of gastrointestinal side effects, such as nausea and vomiting.

Pemvidutide was tested in three different dosages, two of which did not require titration (gradually increasing the dosage), though Aronne suggested that the manufacturer may choose to revisit the dosing details in the future in order to minimize side effects.

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