A Drug to Turn Off the "Appetite Switch": Losing Weight Through a Different Path Than GLP-1 - The Surprising Move of the Epilepsy Medication Topiramate

1｜Core of the News: Epilepsy Drug Stops "Hunger Neurons"

On October 3, 2025, Laval University released news on the theme "Why the Antiepileptic Drug Topiramate Causes Weight Loss," unveiling a new mechanism. The paper was published online on October 2 in the journal Obesity. The research team, in collaboration with UT Southwestern, demonstrated through electrophysiology that the NPY/AgRP neurons, which trigger appetite, are strongly suppressed by topiramate. This action directly puts a brake on the "brain's hunger circuit." ULaval Nouvelles

2｜What's New: The "Route Difference" with GLP-1

GLP-1 agonists (such as Ozempic/Wegovy) primarily reduce food intake by activating pathways that control satiety. In contrast, the target of topiramate, as shown in this study, is the NPY/AgRP neurons that amplify hunger. The study reported that the excitability of these neurons significantly decreased with 1µM of topiramate, and the effect could not be explained by GABA_A receptors alone. The effect was nullified by synaptic transmission inhibition, GABA_B receptor, and K⁺ channel blockade. In other words, the approach is to turn off the hunger engine rather than stepping on the satiety accelerator. PubMed

3｜Profile of the Drug: A Key Component of Qsymia

Originally approved as an antiepileptic drug in the 1990s, topiramate has since expanded its applications to migraine and addiction fields. In the obesity domain, it is marketed in several countries, including the US, as Qsymia, a combination with the appetite suppressant phentermine. Clinical observations report an average weight loss of about 10%, according to the university article. However, the effects vary greatly among individuals, ranging from little to no weight loss to nearly 20% reduction. The clue of "hunger neuron suppression" could be a starting point for understanding these individual differences and tailoring drug use. ULaval Nouvelles

4｜Clinical Landscape: How Effective and Where to Target

Reviews and trials of previous studies suggest a top-line weight loss of around 5-10%, while attention is needed for side effects related to carbonic anhydrase inhibition, including taste changes (such as finding carbonated drinks unpleasant), and central nervous system side effects. Since it affects different pathways than GLP-1, its role in combination or sequence therapy is also being discussed. Depending on the patient profile, the choice between a "satiety-enhancing drug" or a "hunger-reducing drug," or using both as a dual approach, is becoming more realistic. VIDAL

5｜Reactions on Social Media: Quieting "Food Noise" or Facing Side Effects

Reactions on social media were divided. On Reddit, some shared positive experiences, stating "Qsymia quieted the 'food noise' and resulted in over 10% weight loss," while others reported struggling with central side effects like dizziness, drowsiness, and "brain fog." Some users noted that low-dose monotherapy didn't feel effective, while others maintained results after switching from combination therapy to monotherapy. These reactions are anecdotal rather than evidence-based but align with researchers' observations of significant differences between those for whom the drug is effective and those for whom it is not. Reddit

Examples of Reddit Posts (Summary)
・"Qsymia quiets the 'food noise.' About half experience over 10% weight loss." Reddit
・"Topiramate reduced appetite, but dizziness, drowsiness, and brain fog are tough." Reddit
・"25mg doesn't feel effective. Considering increasing the dose." Reddit
・"Lost 9 pounds in a few weeks. Food noise decreased." Reddit

6｜Scope and Limitations of the Research: From Mouse Brains to Human Treatment

The current results are based on electrophysiology in the hypothalamus of mice. Future bridging studies in imaging, genetics, and pharmacology are needed to determine how much of the same neural mechanism is replicated in humans. NPY/AgRP neurons are powerful appetite drivers, and while suppressing them reduces food intake, contributions from other pathways like reward systems and taste changes have been suggested in past literature. Therefore, while "hunger pathway suppression" is an important piece, it is just one part of the overall puzzle. PubMed

7｜The Way Forward: Personalization and "Hybrid Strategies"

With the emerging understanding of circuit differences—satiety with GLP-1 and hunger with topiramate—there is growing potential to explore hybrid dosing designs (combination, sequential switching, low-dose multi-drug) tailored to patient eating behaviors, genetic backgrounds, and comorbidities. In clinical practice, maintaining safety measures such as cautious administration to women of childbearing age and monitoring for psychiatric symptoms is essential, while tuning "which circuit to target and how strongly" becomes the new focus. MDPI