Weight loss research questions need for GLP-1 drugs

A new approach to weight loss research is challenging one of the biggest assumptions behind popular weight loss drugs: Are GLP-1s actually needed to achieve weight loss?

In a new study published April 15 in the journal Molecular Metabolism, researchers tested a drug that targets two other hormones: GIP and glucagon.

The early results, based on studies in mice, rats and monkeys, suggest the approach may lead to similar or even greater weight loss than targeting GLP-1.

“We were captured by the central importance of GLP-1,” study co-author Richard DiMarchi, a professor of chemistry at Indiana University Bloomington, told STAT News.

But he said drugs that target GLP-1 also come with side effects like nausea and vomiting.

And those side effects can limit how much of the drug patients can take.

The new approach removes GLP-1 entirely as a target. Researchers call it “addition by subtraction,” meaning “you’re actually getting to something that’s superior by taking something away,” DiMarchi told STAT News.

To test the idea, scientists ran several experiments.

In one, they gave a triple-G drug to mice that were engineered to lack GLP-1 receptors. The drug led to weight loss similar to what was seen in normal mice, especially at higher doses.

In another test, administering a drug that targets GIP and another targeting glucagon led to greater weight loss than either drug alone. Researchers say this suggests the two hormones may work together to reduce appetite.

In animal studies, an experimental drug targeting both GIP and glucagon led to equal or greater weight loss compared to current treatments, depending on the dose, STAT News reported.

Besides reducing food consumption, it may increase how much energy the body burns.

Researchers also looked at safety. In monkey studies, animals given high doses of the new drug showed no signs of distress. On the other hand, those given existing drugs like Zepbound could not tolerate higher doses.

Results from animal studies do not always translate to people, though. And GLP-1 drugs are known to have heart benefits, which the new drugs may not.

“The data are useful and impressive,” said Randy Seeley, director of the Michigan Nutrition Obesity Research Center, who reviewed the findings.

“It’s a novel way to view the system,” he told STAT News.

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