Scientists Find Way to Enhance Weight Loss from GLP-1 Medications

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Man holding pills and a glass of water - GLP-1 drugs

A new study in mice suggests it is possible to double the weight loss associated with GLP-1 medications by piggybacking certain neuroplasticity-promoting molecules alongside the hormone. The findings were recently published in Nature. Researchers say that GLP-1 hormones can leak through the permeable areas of the blood-brain barrier and serve as ‘Trojan horses ‘.The findings assume that increasing brain plasticity or its ability to change may allow the brain to more readily adapt to weight loss. 

If this mouse study’s findings are replicated in humans, these experimental molecules could super-charge already highly effective GLP-1 drugs for diabetes, cardiovascular disease, and weight-loss drugs such as Wegovy and Ozempic.In addition to potentially increasing the weight-loss effects of GLP-1 drugs, combining them with the plasticity molecules may allow physicians to prescribe lower doses, thus avoiding the nausea that some experience with the current medications. 

Previous research has already said that GLP-1-based drugs can lead to weight loss. The molecule that we have attached to GLP-1 affects the so-called glutamatergic neurotransmitter system, and in fact, other studies with human participants suggest that this family of compounds has significant weight loss potential. 

Scientists believe much of the brain’s functionality has to do with establishing connections between neurons. The ability to form new connections, called neuroplasticity, is mainly active during childhood but continues throughout our lives. The brain shows a remarkable ability to forge new synaptic connections after it is injured, for example, learning to move again after a stroke or traumatic brain injury. 

Researchers say that addressing both neurochemical and behavioural aspects of conditions can be more beneficial. This integrative strategy takes advantage of the brain’s ability to adapt to diverse inputs, leading to more comprehensive and lasting improvements. Combining GLP-1 with the researchers’ molecules is one such combination approach. 

The idea of applying this approach to obesity and weight regulation is very new. This approach is still quite speculative, but something researchers are intensely working on. The thinking is that using a drug to lower body weight and then coupling it with another drug that consolidates the neuronal wiring at this adjusted lower weight might help patients maintain a lower weight. GLP-1 medicines can help one lose weight but it also enhances neuroplasticity which encourages the brain to accept that their new weight is normal. Doctors analyzing this study say that there are some indications that this is how psychoactive substances might be used to treat trauma, or even help recovery from spinal or brain injuries.GLP-1 medications, however, can make their way through structures in the blood-brain barrier called “circumventricular organs,” which are more permeable and “leaky” than the barrier is elsewhere. 

As to whether the researchers’ idea of dual-therapy delivery may apply to other conditions, researchers offered some suggestions. GLP-1 in the brain has been targeted for Parkinson’s, and Alzheimer’s, regulating inflammation, regulating reward behaviors, etc. 

An Alzheimer’s-approved drug, memantine, has shown promising results for binge-eating disorder in a handful of small studies. Memantine is like MK-801 and ketamine, a classical NMDA receptor blocker. However, it is interesting that the GLP-1 system is extremely translatable from mouse to human — at least in terms of the main endpoints of interest here-food intake and body weight.