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Researchers at Tufts University are making strides toward developing a groundbreaking medication aimed at enhancing weight loss while minimizing common side effects associated with existing GLP-1 drugs.
The new drug seeks to surpass the limitations of popular medications like Ozempic by alleviating nausea, muscle loss, and the potential for weight regain. These side effects often accompany treatments aimed at weight management.
Dubbed a “quadruple-action” medication, this innovative drug aspires to help patients achieve a long-term weight loss of up to 30%. This level of effectiveness could rival bariatric surgery, which reduces stomach size and helps individuals manage obesity, according to information released by the researchers.
Semaglutide drugs, which include Ozempic and Wegovy, simulate the effects of the natural hormone GLP-1 (glucagon-like peptide-1). Meanwhile, tirzepatide options like Mounjaro and Zepbound work on both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors.
The Tufts-developed drug takes a different approach by targeting a combination of four hormones: GLP-1, GIP, glucagon, and peptide YY. Each of these hormones plays a crucial role in managing hunger, controlling sugar levels, and promoting fat reduction.
Lead author Tristan Dinsmore, PhD, explains that they designed a unified experimental peptide that mimics all four hormones simultaneously. This method avoids overly stimulating any single hormone and balances the biological systems at work.
“We are not pushing one button too hard,” Dinsmore remarked. “Instead, we’re gently adjusting four ‘dimmer switches’ to effectively manage appetite, blood sugar, and energy utilization.”
Higher doses of GLP-1 and PYY have been known to induce nausea. To mitigate this, researchers incorporated GIP, recognized for its anti-nausea properties, into the drug’s formula. Dinsmore elaborated that GIP signaling not only promotes fullness and blood sugar control but also has effects that can block nausea in preclinical scenarios.
By including PYY along with GLP-1, GIP, and glucagon, the team aims to reduce reliance on the latter hormones to drive weight loss. This could potentially lessen the risk of nausea and high blood sugar, improving the therapeutic outcome.
Currently, the drug remains in the experimental and preclinical research phase, with human trials yet to be conducted.
The findings of this research were published in the Journal of the American Chemical Society.
Dr. Brett Osborn, a Florida-based neurosurgeon and longevity expert, supports the use of GLP-1 medications in weight management. He stated that single-agent GLP-1 drugs, such as Ozempic, demonstrate efficacy for most patients. He emphasized that side effects are typically manageable under the supervision of an experienced healthcare professional.
“We don’t need additional medications to address the same chronic issue affecting people worldwide,” Osborn commented. “Effective GLP-1 agonists are readily available.”
Osborn pointed out that the primary risks associated with GLP-1 medications include muscle loss and malnutrition, which can result from inadequate dietary intake. To combat these issues, he advocates for ensuring sufficient daily protein intake and implementing regular strength training.
For combating obesity, he suggests combining GLP-1 treatments with disciplined nutrition, strength training, adequate hydration, and sufficient sleep. This comprehensive approach can enhance the treatment process.
Sue Decotiis, M.D., a medical weight loss specialist in New York City, noted that managing appetite, metabolism, and fat burning while balancing insulin and blood sugar interactions involves complex physiological functions. She believes that the new drug could assist some patients, but may not be universally effective.
Decotiis emphasized that effective medical weight loss strategies should incorporate monitoring through body composition assessments and ensure adequate protein, fiber, and hydration levels.
The researchers did acknowledge certain limitations inherent in their study. Dinsmore pointed out that their current data derives from cell-based assays rather than from animal studies or human trials. He stated that fine-tuning the safest and most effective balance of the four targeted pathways will necessitate further in-vivo research and clinical trials.
Dinsmore also offered a word of caution to individuals using GLP-1 medications. He advised patients to adhere to the guidance provided by their healthcare providers for optimal results.
This new drug is currently not yet available for public use. However, researchers aim to push the boundaries of therapeutic options by developing a single drug that targets obesity while simultaneously reducing the risk of various associated health complications.
Obesity currently affects over 40% of adults in the United States, and it is linked to numerous health issues including type 2 diabetes, cardiovascular diseases, sleep apnea, and certain cancers. The potential of the new drug, if proven effective, might play a pivotal role in addressing this pressing public health challenge.
“Our motivation is to design a medication that not only targets obesity but also works to prevent a multitude of health issues plaguing society today,” said Krishna Kumar, a co-author and Robinson Professor of Chemistry at Tufts University.
