Repurposing SGLT-2 Inhibitors as a Novel Therapeutic Strategy for Treatment-Resistant Meniere's Disease

Background: Meniere's disease (MD) is a chronic inner ear disorder affecting approximately 0.2% of the population, with 30% of patients remaining refractory to conventional treatments. The pathophysiology involves endolymphatic hydrops, suggesting that agents affecting fluid homeostasis might provide therapeutic benefit. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, originally developed for diabetes, offer unique mechanisms including natriuresis and osmotic diuresis that may address the underlying fluid imbalance in MD. Methods: We conducted a retrospective observational study at the Korea University Anam Hospital, analyzing the medical records of patients with definite MD (Bárány Society criteria) who received off-label empagliflozin 10 mg daily between January 2023 and December 2023. Six patients (3 men, 3 women; mean age 55.8 years) with treatment-resistant MD were identified who had failed conventional therapy for at least 3 months. Primary outcomes included changes in pure tone threshold average (PTA), low-frequency threshold average (LFA), vertigo episode frequency, and vertigo severity using visual analog scale (VAS) scores, assessed at baseline and after 3 months of treatment. Results: All patients demonstrated clinically significant improvements in both auditory and vestibular symptoms. Mean PTA improved from 31.4 dB to 20.8 dB (improvement of 10.6 dB, p < 0.05). Low-frequency hearing showed more substantial recovery, with LFA improving from 37.2 dB to 15.6 dB (improvement of 21.6 dB, p < 0.01). Vertigo frequency decreased dramatically from 1.6 episodes per month to 0.1 episodes per month, with four patients experiencing a complete resolution of vertigo episodes. VAS scores for vertigo severity decreased from 5.2 to 0.5. Treatment was well-tolerated, with only minor adverse effects reported in two patients: transient polyuria in one patient and 5 kg weight loss in another, both consistent with the known pharmacological profile of SGLT-2 inhibitors. Conclusions: This preliminary study suggests a potential clinical benefit of repurposing SGLT-2 inhibitors for treatment-resistant MD. However, the retrospective design and inherent limitations prevent definitive conclusions about causality. The significant improvements observed in both hearing thresholds and vestibular symptoms warrant further investigation through randomized controlled trials with objective outcome measures to establish the true efficacy of this therapeutic approach.