Surgery may no longer be your only best weight-loss option in years ahead

Weight loss treatments remain challenging for individuals. From invasive procedures to prescriptions and off-label drugs with harsh side effects, many still struggle to find a lasting fix to their problem—a challenge now being tackled by scientists from Massachusetts.

Tufts University researchers led by Krishna Kumar, Robinson Professor of Chemistry, have identified a peptide called PYY (peptide tyrosine tyrosine) that, when combined with pre-existing hormones in a weight-loss drug, could deliver lasting weight loss without inducing severe side effects or post-treatment rebound.

PYY, a natural molecule secreted by the gut after eating a meal, helps reduce appetite and slow the process of emptying food from the stomach. Several studies have found that levels of this hormone are inversely linked with body mass index (BMI).

The appetite-suppressing hormone, along with the hormones glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon will comprise the “tetra-functional” clinical candidate developed by the researchers—matching the gold standard of 30 percent weight loss largely associated with bariatric surgery.

Previously used hormones in drug development targeted single pathways. GIP and GLP-1 make an individual feel full after a meal through satiety signals of the brain, while glucagon encourages the body to use stored fat for energy. However, these single-pathway approaches vary in impact from one patient to another.

“By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness,” the Tufts Department of Chemistry visiting scholar Martin Beinborn said.

Beinborn added that multi-chimeric drugs, those that are made up of more than two different types of compound, are inching closer to becoming the next generation of weight loss drugs, rivaling standards set by bariatric surgery.

Bariatric surgery can result in 25 percent to 35 percent loss of body weight, but current qualifications practiced for the surgery only benefit an estimated 1 percent of obese patients with serious health issues, reported the American Society of Metabolic and Bariatric Surgery (ASMBS).

Given what experts consider outdated surgery requirements, the newly developed “quartet drug” will not only make weight loss treatment accessible and milder in side effects, but also complementary to long-term lifestyle change under the medication treatment, without triggering weight gain after drug discontinuation.

Meanwhile, by targeting four hormone receptors: GIP, GLP-1, glucagon, and PYY, the new drug will not just be potent in losing at least 15 to 20 percent of body weight compared to existing prescription drugs like Wegovy and Mounjaro, it will also make balancing nutrition as part of treatment more manageable due to its less harsh side effects.

Aside from promoting weight loss with fewer hindrances, the drug is designed by the scientists to combat weight-related conditions such as type 2 diabetes, cancer, and cardiovascular diseases.
“What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society,” Kumar said.

While a promising feat in the field of weight treatment, the availability of the developed 4-in-1 drug to the public remains uncertain, as it will undergo clinical trials and regulatory approval before manufacturing and distribution.

Despite a breakthrough development, medical practitioners continue to stress the importance of consulting professionals before considering treatment, as eligibility and dosage can vary depending on BMI, overall health, and medical history.

“Losing weight is a choice. But it should never be made because of society’s aesthetic obsession with thinness—or without knowing the full costs,” said Nicholas Cozzi, director of emergency medical services at Rush University Medical Center in Chicago.

Cozzi added, aside from physical symptoms brought by these medications, an often harder problem to diagnose arises—how these medications can mask or worsen behavioral health issues like eating disorders.

Be that as it may, the innovation marks a major step in understanding the human body and harnessing its own mechanism to aid disorder—in this case, providing a lasting treatment for weight loss without the knife.