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A new class of compounds could provide the benefits of gastric bypass surgery without going under the knife or nausea, according to new research presented at the spring meeting of the American Chemical Society (ACS) on March 29. 

But weight loss isn't the only benefit of the potential treatments. According to the researchers, their approach has proven to reduce blood sugar levels as well as opioid cravings. It could also have implications for creating nausea-free chemotherapy drugs. 

Long-term weight loss that mimics surgery

Bariatric surgery, which includes gastric bypass and associated treatments, frequently causes long-term weight loss and even the remission of diabetes. 

But many of the hundreds of millions of obese or diabetic people worldwide cannot access these procedures because they contain risks and aren't fit for everyone.

Now, doctors Robert Doyle and Heath Schmidt - the research's principal investigators- suggest that as an alternative, patients may treat their metabolic issues with a medication that mimics the long-term advantages of surgery.

These advantages are connected to a change in the gut's release of particular hormones, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). They indicate fullness, suppress hunger, and stabilize blood sugar levels after bypass surgery. 

Doyle's team developed a peptide that stimulates two PYY receptors and the GLP-1 receptor. This substance, known as GEP44, made obese rats consume up to 80 percent less food than usual.

The mammals lost an average of 12 percent of their body weight during one 16-day study. That's more than three times the amount lost by rats given liraglutide - an injection solely activates the GLP-1 receptor permitted to treat obesity by the U.S. Food and Drug Administration.

Moreover, there was no evidence of nausea or vomiting in these experiments.

According to the team's most recent findings, GEP44-induced weight loss can also be linked to higher energy expenditure, manifesting as increased activity, heart rate, or body temperature.

Chemotherapy nausea treatment

"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 in a press release. 

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

And that's not all. The duo added that GEP44 lessened rats' desire for opiates like fentanyl. If it also functions in people, Doyle claims, it might be able to aid drug addicts in quitting or preventing relapse.

Additionally, it was discovered that the peptide treatments lower blood sugar, attracting glucose to muscle tissue, which can be used as fuel. They could also transform some pancreatic cells into insulin-producing cells, assisting in replacing those damaged by diabetes. 

Study abstract:

Mechanisms of long-term sustained weight loss and glycemic normalization after obesity surgery have been tied to changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and neuropeptide YY (PYY). We demonstrate that unimolecular peptide biased agonists (GEP44 and GEP12) of the GLP-1-, neuropeptide Y1- and Y2-receptors (GLP-1R; Y1-R, Y2-R) result in Y1-R antagonist controlled, GLP-1R dependent, stimulation of insulin secretion rate in rat and human islets; along with insulin-independent Y1-R mediated glucose uptake in muscle tissue ex vivo; and profound reductions in food intake and body weight relative to liraglutide in a chronic study in obese rats. Our findings support the role of Y1-R signaling in glucoregulation and highlights the therapeutic potential of targeting GLP-1R and both Y1-/Y2-Rs, simultaneously, as a route to ‘bypass’ obesity surgery, while achieving the long-term benefits of such, addressing a need for millions of patients, especially when surgery is not an option.