GLP-1 Drugs’ Surprising Brain Benefits

First introduced as a diabetes medication, GLP-1 drugs quickly took hold for off-label use as weight loss aids, even when the science was still very young.

Here’s one of our first articles on that, back in the day: Semaglutide’s Surprisingly Big Research Gap

As for that popularity? Check out: 1 in 5 US Women Aged 50–64 Has Used GLP-1 RAs: What We’ve Learned

Spoiler, one of the things we’ve learned is: Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why)

Nevertheless, the benefits are plentiful, so it’s worth knowing about. And the latest example of a hitherto-unknown putative benefit is:

Neuroprotectant

Researchers (Dr. Ching-Yang Cheng et al.) examined data from 452,766 adults in the US with an average age of 61, none of whom had epilepsy or seizures at the start of the study, and looked whether GLP-1 medications are associated with a lower risk of developing epilepsy.

In few words: people using GLP-1 drugs were 16% less likely to develop epilepsy over at least five years compared with those using DPP-4 inhibitors (another diabetes drug), after adjusting for factors such as age, high blood pressure, and cardiovascular disease.

Specifically, the GLP-1 drugs included dulaglutide, liraglutide, and semaglutide, with semaglutide showing the strongest association with reduced epilepsy risk. You might be wondering why tirzepatide, a dual GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, did not make the list. The answer is that it was not part of the analysis because it became available after the study period began.

It’s worth noting that for its primary purposes, tirzepatide is more effective than its predecessors, including Ozempic:

❝The first GLP-1 mimicking drug was exenatide (Bayetta). It’s still available for treating type 2 diabetes, but there are currently no generics. Exenatide does provide some weight loss, but this is quite modest, typically around 3-5% of body weight.

For liraglutide, those using the drug to treat obesity will use the stronger one (Saxenda), which typically gives about 10% weight loss.

Semaglutide, with the stronger formulation called Wegovy, typically results in 15% weight loss.

The newest GLP-1 mimicking drug on the market, tirzepatide (Mounjaro for type 2 diabetes and Zepbound for weight loss), results in weight loss of around 25% of body weight.❞

Read in full: Ozempic’s cousin drug liraglutide is about to get cheaper. But how does it stack up?

You can also read more about tirzepatide in our main feature about it, here: Mounjaro/Zepbound’s Stable Weight Loss Curve

Back to the more recent study, this (about the reduced epilepsy risk) is an important finding, because it suggests GLP-1 drugs may have neurological effects beyond blood sugar control.

You can find the paper itself, here: Association Between GLP-1 Receptor Agonist Use and Epilepsy Risk in Type 2 Diabetes

And for more on GLP-1 drugs and the brain (albeit in the other direction), see: How Your Emotions Affect GLP-1 Drug Results!

A possible connection?

This is extra interesting too, because the ketogenic diet, which also affects glycemic control albeit by a completely different mechanism, was first conceived for the treatment of children with refractory epilepsy. By starving the body (including the brain) of glucose, the liver must convert fat into fatty acids and ketones, which latter the brain (and indeed the rest of the body) can now use for energy instead of glucose, thus avoiding one of the the main triggers of refractory epilepsy in children.

^{Source: The Ketogenic Diet: One Decade Later | Pediatrics}

Even the pediatric epilepsy studies, however, conclude the keto diet does have unwanted side effects, such as kidney stones, constipation, high cholesterol, and acidosis, so the ketogenic diet is far from a substitute to medical treatments that don’t have such risks.

You can read more about that here: Ketogenic Diet: Burning Fat Or Burning Out?

Want to learn more?

You might like this book that we reviewed a little while back:

Magic Pill: The Extraordinary Benefits and Disturbing Risks of the New Weight-Loss Drugs – by Johann Hari

Enjoy!