New weight loss treatment ‘could be like gastric band surgery with no knife’

·3-min read
The new treatments could hold out hope to obese patients. (Getty)
The new treatments could hold out hope to obese patients. (Getty)

A new class of weight-loss treatments could offer the benefits of gastric band surgery, without requiring patients to go under the knife.

In animal tests, the injectable compounds have already been shown to cause animals to lose weight, and lower blood glucose.

The injectable compounds also avoid the side effects of nausea and vomiting that are common with current weight-loss and diabetes drugs.

The new treatment not only reduces eating but also boosts calorie burn, according to scientists.

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The researchers are presenting their results at the spring meeting of the American Chemical Society (ACS).

"Obesity and diabetes were the pandemic before the COVID-19 pandemic," says Robert Doyle, PhD, one of the two principal investigators on the project, along with Christian Roth, MD.

"They are a massive problem, and they are projected to only get worse."

Gastric bypass and related procedures, known collectively as bariatric surgery, offer one solution, often resulting in lasting weight loss and even remission of diabetes.

But surgery is not suitable for everybody.

As an alternative, Doyle says, they could tackle their metabolic problems with a drug that replicates the long-term benefits of surgery.

Those benefits are linked to a post-bypass-surgery change in the gut's secretion levels of certain hormones—including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)—that signal fullness, curb appetite and normalise blood sugar.

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Current drugs that aim to replicate this effect primarily activate cellular receptors for GLP-1 in the pancreas and brain.

That approach has shown great success in reducing weight and treating type 2 diabetes, drawing a lot of social media postings from celebrities in recent months.

But many people can't tolerate the drugs' side effects, said Doyle. "Within a year, 80 to 90% of people who start on these drugs are no longer taking them," he added.

To address that drawback, various researchers have designed other treatments that interact with more than one type of gut hormone receptor.

Doyle's group created a peptide that activates two receptors for PYY, as well as the receptor for GLP-1. Dubbed GEP44, this compound caused obese rats to eat up to 80% less than they would typically eat.

By the end of one 16-day study, they lost an average of 12% of their weight.

That was more than three times the amount lost by rats treated with liraglutide, an injected drug that activates only the GLP-1 receptor and that is approved by the US Food and Drug Administration for treating obesity.

In contrast to liraglutide, tests with GEP44 in rats and shrews (a mammal that, unlike rats, is capable of vomiting) revealed no sign of nausea or vomiting, possibly because activating multiple receptors may cancel out the intracellular signalling pathway that drives those symptoms, Doyle says.

"For a long time, we didn't think you could separate weight reduction from nausea and vomiting, because they're linked to the exact same part of the brain," Doyle said

But the researchers have now uncoupled those two pathways – and that has implications for chemotherapy, which causes similar side effects.

Doyle said: "What if we could maintain the benefit of chemotherapy drugs but tell the part of the brain that causes vomiting and nausea to knock it off? Then we could dose patients at a higher level, so they would have a better prognosis, and they would also have a better quality of life while undergoing chemotherapy."

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