No surgery, no side effects: New drug shows promise in fighting obesity and diabetes

A promising new treatment for obesity has emerged that offers significant weight loss without the need for surgery or the unpleasant side effects of nausea and vomiting.

This innovative approach involves a new class of compounds that has shown dramatic results in lab animals, including reducing weight and lowering blood glucose levels.

Additionally, the injectable compounds have demonstrated an ability to boost calorie burn while also reducing eating.

The findings from this groundbreaking research will be presented at the upcoming ACS Spring 2023 meeting by the team of scientists behind this exciting new treatment.

“Obesity and diabetes were the pandemic before the COVID-19 pandemic,” adds lead author Robert Doyle. “They are a massive problem, and they are projected to only get worse.”

Bariatric surgery, which includes gastric bypass and related procedures, has been a viable option for weight loss and diabetes remission, often with lasting effects. However, these surgeries come with risks and are not suitable for everyone, leaving many of the millions of obese or diabetic individuals worldwide without access to this solution. As an alternative, Doyle suggests using a drug that replicates the long-term benefits of surgery to tackle metabolic problems.

The benefits of gastric bypass surgery are linked to changes in the gut’s secretion levels of hormones, such as GLP-1 and PYY, which signal fullness, reduce appetite, and regulate blood sugar. While current drugs that aim to replicate these effects primarily activate cellular receptors for GLP-1 in the pancreas and brain, they often come with unwanted side effects. Despite the success of these drugs in reducing weight and treating type 2 diabetes, many people cannot tolerate the associated side effects, according to Doyle.

To overcome this challenge, researchers have been developing alternative treatments that target multiple types of gut hormone receptors. One such treatment is a peptide created by Doyle and his team, which activates two receptors for PYY and the GLP-1 receptor.

The peptide, known as GEP44, has shown remarkable results in animal studies, with obese rats consuming up to 80% less food than normal and losing an average of 12% of their weight in a 16-day study. In comparison, rats treated with liraglutide, an FDA-approved drug for obesity that activates only the GLP-1 receptor, lost just a third of that amount.

Additionally, tests with GEP44 on rats and shrews, which are capable of vomiting, did not result in any signs of nausea or vomiting. According to Doyle, this could be due to the activation of multiple receptors, which may counteract the intracellular signaling pathways that lead to these unpleasant side effects.

The latest results from Doyle’s team reveal that GEP44, the peptide treatment that activates multiple receptors for PYY and GLP-1, not only reduces eating but also leads to higher energy expenditure. This increase in energy expenditure can manifest in the form of greater movement, heart rate, or body temperature.

While GEP44 has a short half-life in the body of approximately one hour, Doyle’s group has designed a next-generation peptide with a much longer half-life, allowing for once or twice-weekly injections instead of multiple daily injections. Furthermore, the researchers report that rats treated with this new compound maintain their slim physique even after treatment ends, a rare outcome with currently approved drugs.

The benefits of peptide treatments extend beyond weight loss. They also lower blood sugar by directing glucose into muscle tissue for use as fuel and converting certain cells in the pancreas into insulin-producing cells, which can help repair damage caused by diabetes.

Moreover, Doyle and Schmidt have discovered that GEP44 can reduce cravings for opioids such as fentanyl in rats, which could be beneficial in helping addicts recover from their addiction or prevent relapse.

The researchers have applied for patents on their compounds and plan to test them on primates.

They will also examine the impact of these treatments on gene expression and brain function and how they could be used in conjunction with other types of medication.

“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 adds.

The researchers have successfully disentangled the pathways that cause weight loss and nausea, which could have significant implications for chemotherapy, as it often induces similar side effects.

“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,” he points out.

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