A year after stopping GLP-1 therapy, patients regain two thirds of their lost weight, according to a 2022 study. Part of the reason may be that each of us has a ‘set weight’ – a baseline weight, likely determined by a mix of genetic, environmental and preferential factors, which our bodies do everything to stick to.

Some researchers are trying to hijack that set weight. In a paper published in Nature in May 2024, scientists at the Novo Nordisk Foundation Center for Basic Metabolic Research presented mouse studies of a compound, attached to GLP-1, which uses the hormone to target NMDA receptors in the brain involved in appetite control and neuronal plasticity. The idea is to potentiate GLP-1s appetite-suppressing effects by smuggling in a molecule that blocks the excitatory NMDA receptors, and which may help lower set-weight.

“Studies have shown than even infrequent treatment [with NMDA receptor blockers] can lead to persistent changes to the brain pathologies,” said author Christoffer Clemmensen, co-founder of University of Copenhagen spin-out Ousia Pharma. The hope is that potentiating GLP-1 agonism in this way could allow lower doses and longer-lasting weight loss.

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