New treatment may aid weight loss without side effects

Share on PinterestCould a novel obesity treatment currently under study bring weight loss while avoiding common side effects? Image credit: Yoshiyoshi Hirokawa/Getty Images.

• Researchers have developed a new class of peptides that could provide the benefits of gastric bypass surgery without the need for invasive procedures.
• According to new research, these peptides contributed to significant weight loss and reduced blood glucose levels in rat models of obesity.
• The injectable compounds avoid the side effects of nausea and vomiting commonly experienced with current weight loss and diabetes drugs, and reduce eating while also increasing calorie burn.

Obesity and diabetes are serious public health concerns, and the former is one of the top risk factors for diabetes.

Bariatric surgery — which includes gastric bypass, gastric sleeve, and gastric band — is a viable treatment option, as it can result in sustained weight loss and even the remission of diabetes.

However, these procedures come with potential hazards, are not suitable for everyone, and are not readily available to most people.

Now, some researchers suggest that another treatment option could be to address metabolic issues through medication that emulates the long-term advantages of surgery.

After undergoing gastric bypass surgery, some people experience certain health benefits that are associated with changes in hormone secretion by the gut.

The hormones involved, including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), signal fullness, reduce appetite, and help control blood sugar levels.

Researchers have developed drugs that aim to replicate these effects by targeting GLP-1 receptors in the pancreas and brain.

These drugs have shown success in reducing weight and treating type 2 diabetes. Unfortunately, some people are unable to tolerate the side effects of these drugs, and studies show that almost half of those who start taking them stop within a year, so there is a need for better options with fewer side effects.

A team led by researchers from Syracuse University, NY, has developed a new peptide with the aim of addressing this need. They presented their recent research at the ACS Spring 2023 meeting, which took place between March 26–30.

The researchers propose that a compound that mimics the long-term benefits of gastric bypass surgery could be an alternative solution to help people with metabolic problems.

Researchers have developed different approaches to address the side effects of drugs that target only one hormone receptor in the gut. One method is to design treatments that interact with multiple types of receptors.

In a previous study, the team created a peptide called GEP44, which activates two receptors for peptide YY and one receptor for glucagon-like peptide-1.

They tested this compound on rats with obesity, and they found that the rats that received GEP44 ate up to 80% less than they typically would, and they lost an average of 12% of their weight within a 16-day study period.

Their recent study compared the effectiveness of the new peptide GEP44 to an existing drug, liraglutide, for treating obesity.

The study found that rats treated with GEP44 lost more weight than those treated with liraglutide. GEP44 did not cause any signs of nausea or vomiting, unlike liraglutide, when tested on rats and shrews.

The researchers suggest that this may be due to GEP44 activating multiple receptors, which could prevent the intracellular signaling pathway that causes these symptoms.

This study also indicates that the weight loss caused by GEP44 is not solely due to reduced food intake but is also a result of increased energy expenditure. This increase in energy expenditure can manifest in various ways, such as higher physical activity, heart rate, or body temperature.

The peptide treatments, such as GEP44, not only help with weight loss but also aid in reducing blood sugar levels by directing glucose into muscle tissue to be used as fuel and by converting certain cells in the pancreas into insulin-producing cells.

GEP44 has a short half-life in the body and needs to be injected several times a day to remain effective. However, the team has developed a new peptide that has a much longer lifespan, meaning it only needs to be injected once or twice a week.

The researchers found that rats treated with this new compound maintain their weight loss even after the treatment has ended, which is not usually the case with current drugs approved for obesity treatment.

Dr. Becca Krukowski, professor of public health sciences at the University of Virginia, not involved in this research, told Medical News Today that “obesity is clearly a growing concern worldwide.”

“To address this concern, it is important to have an array of treatment options, in order to have options that work for individuals with different circumstances — such as distance to health care — and with different preferences,” she noted.

“Surgical weight loss treatments have made significant strides in the past 20 years, and pharmacological weight loss treatments have dramatically improved in the last 5 years or so. However, surgical options are not appealing for some individuals, and the current pharmacologic treatment have drawbacks such as cost, mode of administration (such as injections), frequency of administration, side effects, and weight regain after discontinuing treatment. It will be important to have new treatment strategies that address these barriers, so that treatment for obesity is more accessible.”

– Dr. Becca Krukowski

Haley Bishoff, a nutrition expert from Rūtsu Nutrition, also not involved in the study, highlighted that healthcare providers should also focus on addressing the key issues behind obesity and diabetes, in addition to developing new treatment options.

“A major concern with bariatric surgery is long-term nutritional deficiencies from lack of caloric intake and decreased nutrient absorption. This is especially true for micronutrients such as iron, vitamin B12, vitamin D, and calcium,” Bishoff told MNT, highlighting previous research on the topic.

“Bariatric surgery decreases appetite and reduces eating. Prescription drugs that mimic this effect may contribute to people not meeting their basic nutrition needs. Alleviating nausea and vomiting is a major upside. However, these treatments don’t solve the issue of potential long-term nutritional deficiency, nor do they teach people how to create healthy lifestyle habits,” Bishoff explained.

Dr. Krukowski noted that “while these are early findings in lab animals, this research may lead to new medications that are safe and effective for patients over time.”

“But first, this medication would need to proceed through the intentionally slow and careful multi-stage and multi-year testing process that would be required prior to being broadly prescribed,” she cautioned.

Nevertheless, Krukowski added, “[t]he potential lack of weight regain after discontinuing treatment would be particularly exciting if this treatment characteristic was confirmed in testing with humans.”

Bishoff highlighted that this research could potentially have both positive and negative outcomes: “The positives being that people can take smaller doses of drugs that can provide desired outcomes while reducing nausea and vomiting side effects. On the flip side, it’s possible that weight loss drugs reduce caloric intake to the point of deficiency or malnutrition.”

Ultimately, further research is needed and will likely take several years.

“Weight loss drugs may have their medical benefits but it’s important that patients recognize these drugs should not be used to replace a healthy lifestyle. They can be seen as a tool versus a solution. Eating a variety of well-balanced meals, meeting daily caloric goals, and participating in regular physical activity should always be encouraged when managing weight and diabetes. “

– Haley Bishoff

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