Researchers aim to minimise side effects of obesity medications through groundbreaking study

A pioneering £1.2 million research initiative is now underway at University College London (UCL) and the Rowett Institute at the University of Aberdeen, seeking to refine the effectiveness of weight-loss medications while reducing their associated side effects. The study, funded by the Medical Research Council, will investigate the precise mechanisms through which these drugs act in the brain, with the goal of developing improved treatments that minimise discomfort while maximising therapeutic benefits.

The Promise and Challenges of Semaglutide

Semaglutide, an anti-diabetic medication marketed under brand names such as Wegovy and Ozempic, has gained widespread recognition for its ability to support weight management. The drug works by acting on the brain to reduce food intake, helping people with obesity or overweight to achieve significant weight loss.

However, despite its effectiveness, semaglutide can produce unpleasant side effects, including nausea and vomiting. These adverse reactions can make it difficult for individuals to adhere to long-term treatment, ultimately reducing the drug’s overall effectiveness in managing weight.

Investigating the Brain’s Role in Drug Response

Leading the study are Professor Lora Heisler of the Rowett Institute and Professor Stefan Trapp of UCL Biosciences, who will spend the next three years mapping out how semaglutide interacts with the brain. Their research will focus on identifying specific neural pathways that influence different aspects of eating behaviour, such as reducing meal size, encouraging healthier food choices, slowing digestion, and diminishing the brain’s reward response to highly palatable foods.

Crucially, the study will also examine the pathways responsible for triggering nausea and other unwanted side effects. By distinguishing between these different mechanisms, the researchers aim to uncover ways to modify how the drug acts in the brain, potentially paving the way for future medications that retain semaglutide’s benefits without the drawbacks.

Aiming for More Effective and Tolerable Treatments

Professor Trapp highlighted the importance of this research in advancing obesity treatment, “While semaglutide and similar drugs have been very effective in helping people with diabetes and show much promise in helping people to lose weight, we still do not know that much about how exactly they work in the brain.”

He noted that his laboratory has conducted extensive studies on the glucagon-like peptide-1 receptor (GLP-1R), the brain target of semaglutide. By mapping out the drug’s mechanism in greater detail, Trapp and his team hope to contribute to the development of more refined medications with fewer adverse effects.

Professor Heisler further emphasised the potential impact of their findings, “There is huge interest in how the brain targets of semaglutide and similar drugs could be switched on in a slightly different or more targeted way. Drugs that can do this could work better, have effects that last longer, and produce specific therapeutic obesity treatment benefits without the nausea side effect.”

She also pointed out that such research is only possible due to recent technological advancements, stating, “We can only now do these types of studies because of the latest technological advances, and we expect our results will provide the blueprint to develop even better obesity medications in the future.”

Implications for Future Obesity Treatments

This study could play a crucial role in shaping the next generation of obesity medications, offering new treatment options that are not only effective but also better tolerated. As more people turn to pharmacological treatments for weight management, research like this is essential to ensuring that these interventions remain both accessible and sustainable for long-term use.

By deepening the scientific understanding of how semaglutide works in the brain, researchers at UCL and the Rowett Institute aim to refine and improve the treatment landscape, ultimately providing more effective and tolerable solutions for individuals seeking to manage their weight through medical therapy.