For as long as drugmakers have been testing weight-loss drugs, the question has been: How much weight do people lose? Now it is changing to: What kind of weight are they losing?

Rapid weight loss can come with a downside-people can end up injured or prone to falls if they shed significant muscle alongside fat. Drugmakers are testing a new generation of muscle-protecting and body fat-targeting drugs to fix that.

At a medical conference in Milan this week, mid- and late-stage studies from companies like Novo, Eli Lilly and Regeneron indicated that several drug candidates may be able to better preserve muscle and help shed problematic belly fat.

If proven out, these experimental medications could ultimately improve people's health while they rapidly lose weight on these therapies. It would also give drugmakers a powerful argument for doctors to prescribe-and health insurers to pay for-a new set of drugs. "I'd rather have more fat loss and slightly less weight loss, but retain more muscle," said Dr. Juan Pablo Frías, an endocrinologist who was involved in new research presented by Eli Lilly, and who has worked with other companies. "I want you to be able to bend down and tie your shoe without difficulty."

Regeneron reported mid-stage data on a drug it is developing to preserve muscle when taken alongside a GLP-1. The study found that people taking the drug lost about two-thirds to three-quarters less thigh muscle than those taking semaglutide alone. Over 26 weeks, the highest doses of the drug roughly halved the loss of lean mass, which includes muscle, compared with those who only took semaglutide, the active ingredient in Ozempic and Wegovy.

This is especially critical for older adults, particularly as many more gain access to weight-loss drugs through Medicare. But doctors stress that body composition matters for younger adults, too, who risk losing muscle when they rapidly shed weight, increasing the chances of injuries or conditions such as osteoporosis later in life.

As the weight-loss drug market has taken shape over the past few years, the dominant players, Eli Lilly and Novo Nordisk, have been marketing drugs that lead patients to lose, on average, 20% or more of their weight over about a year and a half at the highest doses. Now companies need to differentiate their drugs in other ways, doctors, researchers and analysts say.

Novo is studying whether one of its experimental drugs, CagriSema, can cut belly fat as it helps people lose weight. The treatment is an obesity shot that combines the main ingredient in Ozempic and Wegovy with cagrilintide, a compound that mimics the appetite-regulating hormone amylin.

In research presented this week at the European Association for the Study of Diabetes annual meeting, Type 2 diabetes patients taking CagriSema lost 14.3% of their body weight over roughly nine months on average and had less fat around their liver and pancreas when compared with those on a placebo. Fat in and around these organs leads to a higher risk of heart disease and other health problems. The company also studied, using brain scans, the drug's effects on patients' thoughts and cravings for food.

"Understanding pain, understanding food noise, understanding something that actually affects you every day, can become differentiators," said Martin Holst Lange, Novo's chief scientific officer. "How does that weight loss make you feel?"

The differentiation is increasingly important as the field gets more competitive. International patent applications for GLP-1s rose 28% in the 12 months to March 2026, according to an analysis by law firm Pinsent Masons.

Lilly also presented new data on its experimental next-generation weight loss drug retatrutide, which helped patients lose as much as 28.3% of their weight on average in an earlier study. In the new study, patients self-reported better everyday movement while taking the drug when compared with those on the placebo.

"We now routinely measure functional outcomes in terms of muscle strength or activity in these clinical trials, and we usually see a very significant benefit," said Dan Skovronsky, Lilly's chief scientific officer.

Other experts caution that the metrics in these trials don't always tell the full story about patients' health.

Wei Shen, an assistant professor at Columbia University and body composition researcher, said lean mass shouldn't be equated with muscle, because it includes other non-fat tissues in addition to muscle. Improvements in self-reported questionnaires don't prove that patients maintain their muscle, other experts said.

"It's going to take time to learn what data we should be tracking and focus on the right outcomes," said Dr. Nidhi Kansal, an obesity medicine doctor at Northwestern Medicine. "We call them weight-loss drugs, but the goal medically is fat loss."