Obesity and diabetes are major health concerns worldwide, affecting millions of people and resulting in a range of serious health problems, including heart disease and strokes.
While bariatric surgery, such as gastric bypass, can offer a long-term solution for weight loss and diabetes remission, it is not suitable for everyone and carries big risks.
Researchers are now exploring the potential of a new class of compounds that could offer the same benefits as gastric bypass surgery without the need for invasive procedures.
According to a recent study from the Queen Mary University of London, researchers have developed injectable compounds that can dramatically reduce weight and lower blood glucose levels in lab animals.
These potential treatments also avoid the side effects of nausea and vomiting that are common with current weight-loss and diabetes drugs.
The compounds work by mimicking the long-term benefits of surgery, which are linked to changes in the gut’s secretion levels of certain hormones that signal fullness, curb appetite and normalize blood sugar.
Current drugs that aim to replicate this effect primarily activate cellular receptors for glucagon-like peptide-1 (GLP-1) in the pancreas and brain, but many people cannot tolerate the drugs’ side effects.
To address this issue, various researchers have designed other treatments that interact with more than one type of gut hormone receptor.
For example, the researchers at the Queen Mary University of London created a peptide called GEP44 that activates two receptors for peptide YY (PYY), as well as the receptor for GLP-1.
In obese rats, this compound caused a reduction in food intake of up to 80% and led to an average weight loss of 12% in just 16 days.
This was more than three times the amount lost by rats treated with liraglutide, an injected drug that activates only the GLP-1 receptor and is approved by the U.S. Food and Drug Administration for treating obesity.
Importantly, 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 signaling pathway that drives those symptoms.
Moreover, the weight loss caused by GEP44 can be traced not only to decreased eating but also to higher energy expenditure, which can take the form of increased movement, heart rate, or body temperature.
The researchers have now designed a peptide with a much longer half-life, meaning it could be injected only once or twice a week instead of multiple times a day.
Rats treated with this next-generation compound keep their new, slimmer physique even after treatment ends, which often isn’t the case with currently approved drugs.
These compounds also reduce blood sugar by pulling glucose into muscle tissue, where it can be used as fuel, and by converting certain cells in the pancreas into insulin-producing cells, helping replace those that are damaged by diabetes.
Another potential benefit of GEP44 is that it reduces the craving for opioids such as fentanyl in rats, which could help addicts quit illicit drugs or fend off a relapse.
If this works in humans, it could have significant implications for the treatment of addiction.
The researchers have filed for patents on their compounds and plan to test their peptides in primates.
They will also study how the treatments change gene expression and rewire the brain, and what that could mean for these compounds, as well as other types of medication.
This research has the potential to offer a safe, effective, and accessible alternative to bariatric surgery for people struggling with obesity and diabetes.
If you care about weight management, please read studies about diets that could boost your gut health and weight loss, and 10 small changes you can make today to prevent weight gain.
For more information about weight loss, please see recent studies that Mediterranean diet can reduce belly fat much better, and Keto diet could help control body weight and blood sugar in diabetes.
The study was conducted by Robert Doyle et al and presented at ACS Spring 2023.
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