Semaglutide without the sickness?

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Semaglutide, which acts in the brain to reduce food intake, has fast become one of the most effective pharmaceutical weapons in the global battle against obesity.

GLP1-based obesity medicines are the subject of intense public debate as governments seek to harness their public health potential.

But semaglutide’s positive impact on weight loss is sometimes offset by nausea and vomiting, which can reduce its benefits by putting patients off sticking to a course of treatment.

Now a team led by Professor Lora Heisler of the University of Aberdeen’s Rowett Institute and Professor Stefan Trapp at UCL – funded by the Medical Research Council – will spend three years identifying where semaglutide acts in the brain to influence specific aspects of food intake such as meal size, healthier food choices, delaying digestion and dampening the “feel-good” food effect, and also where it acts to produce the unpleasant nausea side effects.

The project will involve careful statistical analysis of the resulting data by research colleagues from Biomathematics and Statistics Scotland (BioSS).

Answering these questions will fill large gaps in our current understanding of precisely how the drug works.

Professor Heisler’s laboratory at the Rowett Institute recently identified a cluster of brain cells that can be harnessed to reduce food intake and body weight – without the nausea, the common side effect of this class of obesity medicines.

Speaking about the new project, Professor Heisler said: “There is huge interest in how the brain targets of semaglutide (Wegovy) and similar drugs such as tirzepatide (Mounjaro) 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.

“This research could also lead to new drugs that are produced as pills instead of injectables, thereby reducing costs and increasing availability.

“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. ”

Professor Trapp added: “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.

“My lab has done extensive research for years into the glucagon-like peptide-1 receptor (GLP-1R) in the brain, which semaglutide targets, so we hope by mapping out the drug’s mechanism more precisely, we will be able to develop more effective drugs with fewer side effects.”