A novel family of chemicals may be able to provide the advantages of gastric bypass surgery without the need for surgery. These possible therapies drastically lower laboratory animal body weight and blood glucose levels.
Also, the injectable chemicals do not cause nausea or vomiting, which are frequent adverse effects of today’s diabetic and weight-loss drugs. Experts now claim that the new therapy enhances calorie burn while also decreasing eating.
The researchers presented their findings at the American Chemical Society’s spring conference (ACS). More than 10,000 presentations on a variety of research subjects are included at the hybrid ACS Spring 2023 conference, which runs from March 26 to 30.
According to Robert Doyle, Ph.D., one of the two major investigators on the project together with Christian Roth, M.D., “Obesity and diabetes were the pandemic preceding the COVID-19 pandemic.” They pose a significant issue, and the future seems grim.
One option is bariatric surgery, which includes the gastric bypass and associated operations. It often leads to long-lasting weight reduction and even the remission of diabetes. Yet many of the hundreds of millions of obese or diabetic individuals throughout the globe cannot access these procedures because they are risky, not fit for everyone, and contain risks. Doyle suggests 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 shift in the gut’s release of particular hormones, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which indicate fullness, suppress hunger, and stabilise blood sugar levels after bypass surgery. The pancreas and brain have GLP-1 receptors that are predominantly activated by the current medications designed to mimic this action. Celebrities have been posting often on social media recently about this method, which has had excellent success treating type 2 diabetes and helping people lose weight. Yet according to Doyle, many patients cannot handle the adverse effects of the medications. Roth is at Seattle Children’s Research Center and Doyle is at Syracuse University and SUNY Upstate Medical University; “After a year, 80 to 90% of patients who start on these medications are no longer using them.”
Several medicines have been developed by different researchers that interact with many types of gut hormone receptors in order to overcome that limitation. For instance, Doyle’s team developed a peptide that stimulates two PYY receptors as well as the GLP-1 receptor. This substance, known as GEP44, made obese rats consume up to 80% less food than they normally would. They dropped an average of 12% of their body weight during the course of one 16-day research. There was more than three times the amount of weight loss in rats given liraglutide, an injectable medication that solely stimulates the GLP-1 receptor and is authorised in the United States. for treating obesity, the Food and Drug Administration.
In contrast to liraglutide, studies using GEP44 in rats and shrews (a species capable of vomiting, unlike rats) showed no signs of nausea or vomiting. Doyle theorises that this may be because activating several receptors may balance out the intracellular signalling pathway that causes such symptoms.
In its most recent findings, his team is now revealing that the weight loss brought on by GEP44 may be linked to increased energy expenditure, which can manifest as increased exercise, heart rate, or body temperature, in addition to reduced eating.
GEP44 only has a half-life of around an hour in the body, but Doyle’s team has just created a peptide with a substantially longer half-life. It might thus be injected only once or twice a week as opposed to many times every day. In contrast to often the situation with already licenced medications, Doyle notes that the researchers are now finding that rats treated with this novel substance maintain their new, smaller physique long after therapy is finished.
Yet, the peptide therapies have other advantages than weight reduction. Also, they lower blood sugar levels by transporting glucose into muscle tissue, where it may be utilised as fuel, and by transforming certain pancreatic cells into insulin-producing cells, therefore assisting in the replacement of those that have been harmed by diabetes. Another advantage is that GEP44 lessens rats’ appetite for opiates like fentanyl, according to a recent study by Doyle and Heath Schmidt of the University of Pennsylvania. Doyle claims that if it is successful in people, it may be able to aid drug users in quitting their addiction or prevent relapse.
The scientists want to test their peptides in monkeys and have applied for patents on their substances. They will also investigate how the medications alter gene expression and reorganise the brain, and what implications that may have for these substances and other kinds of drugs.
As Doyle notes, “We didn’t believe you could separate weight loss from nausea and vomiting for a long time since they’re related to the exact same portion of the brain.” But now that the two mechanisms have been decoupled, there are implications for chemotherapy, which has a similar set of adverse effects. What if we could keep chemotherapy medications working, yet instruct the brain region that triggers nausea and vomiting to back off? So that they may have a better prognosis and a better quality of life while receiving chemotherapy, we could then dose them at a greater level,” he explains.
