By Samuel A. Collazo, MD; Thomas M. Kaffenberger, MD; and Ryan J. Soose, MD
With the recent advent of Aura6000, there are now three Food and Drug Administration (FDA)- approved hypoglossal nerve stimulation (HGNS) devices for the treatment of patients with moderate-to-severe obstructive sleep apnea (OSA) who have failed positive airway pressure (PAP) therapy. As the name suggests, HGNS therapy works by electrically stimulating select branches of the hypoglossal nerve, leading to tongue protrusion and airway opening. The HGNS implantation surgery is an outpatient procedure performed under general anesthesia, and its anatomy-sparing approach significantly reduces the traditional surgical risks and postoperative recovery time associated with craniofacial and pharyngeal airway reconstructive surgeries.1
The first of these surgically implanted but medically managed devices is the Inspire device (Inspire Medical Systems Inc.), approved in 2014. Since then, more than 120,000 patients have been implanted, and hundreds of peer-reviewed publications have firmly established HGNS as a treatment modality in the OSA space. This literature includes the ADHERE Registry, a sponsored, multicenter, international registry of 5,000 HGNS patients treated across 61 centers in the U.S. and Europe. The final results of the ADHERE Registry were presented at the SLEEP 2026 annual meeting of the APSS and reported apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS) improvements in line with the STAR trial, as well as favorable objective therapy adherence rates.
A bilateral hypoglossal nerve stimulator, the Genio 2.1, (Nyxoah SA), was approved in 2025, and several months ago, a new unilateral hypoglossal nerve stimulator, the Aura6000 (LivaNova), received FDA approval in 2026. This article provides an overview comparing the design and clinical features of these devices (Table 1), as well as highlighting the pivotal trial data that preceded approval (Table 2). The data presented in these tables were retrieved from the “Stimulation Therapy for Apnea Reduction” trial (STAR; Inspire), the “Dual-sided Hypoglossal NeRvE StimuLatIOn for the TreatMent of Obstructive Sleep Apnea” trial (DREAM; Genio), and the “Treating Obstructive Sleep aPnea using taRgEted hYpoglossal nerve stimulation” trial (OSPREY; Aura6000), in addition to device manuals available online. These HGNS trials all exhibited clinically meaningful improvements in both patient-reported and polysomnographic OSA outcomes, along with acceptable safety and side effect profiles.
Table 1: Hypoglossal nerve stimulation device comparison
| Inspire V | Genio 2.1 | Aura6000 | |
|---|---|---|---|
| Mechanism of Action | Unilateral Distal HGNS; respiratory synchronized | Bilateral Distal HGNS; asynchronous | Unilateral Proximal HGNS; asynchronous |
| AHI Range (events/hour) | 15-100 | 15-65 | 15-65 |
| Age Range (years) | 18+* | 22-75 | 22-75 |
| Maximum BMI (kg/m²) | 40 | 32 | 35 |
| DISE to exclude CCC | Yes | Yes | No |
| Incision(s) | 2 (Neck + Chest) | 1 (Neck) | 2 (Neck + Chest) |
| Hardware Design
Implanted External |
IPG + Cuff-based Stimulation Lead
Remote control |
Bilateral Paddle-based Implantable Stimulator
Disposable Patch and Rechargeable Wearable |
IPG + Cuff-based Stimulation Lead
Remote control |
| Generator vs Wearable | Generator | Wearable | Generator |
| Charging? | No | Daily | Every 2 days |
| IPG Battery Life | 10 years | N/A | 15 years |
| MRI Compatibility | Conditional 1.5/3T | Conditional 1.5/3T | None |
*Inspire is also FDA approved for patients with Down Syndrome (Trisomy 21) who are 13 years or older
** Abbreviations: BMI (body mass index), CCC (complete concentric collapse at the palate), DISE (drug-induced sleep endoscopy), IPG (implantable pulse generator), MRI (magnetic resonance imaging), and ODI (oxygen desaturation index)
Table 2: Hypoglossal nerve stimulation pivotal clinical trial comparison
| Inspire (STAR) |
Genio (DREAM) |
Aura6000 (OSPREY) |
|
|---|---|---|---|
| AHI Response a | 66% | 64% | 58% |
| ODI Response b | 75% | 71% | 69% |
| Δ Median AHI4% | 29.3 → 9.0 | 24.3 → 6.8e | 34.3 → 11.0 |
| Δ Median ODI4% | 25.4 → 7.4 | 22.8 → 5.9e | 34.9 → 11.1 |
| Δ Median ESS | 11.0 → 6.0 | 10.0 → 5.0e | 10.0 → 6.0 |
| Surgical re-interventions c | 2% | 3% | 11% |
| Study Design | Multicenter, single group, prospective cohort → randomized, controlled therapy-withdrawal trial | Multicenter, single group, prospective cohort | Multicenter randomized clinical trial → 6-month open label extension |
| Mean BMI (kg/m²) | 28.4 | 28.5 | 30.6 |
| DISE screen? d | Yes | Yes | No |
a AHI responders achieved a minimum of 50% reduction in 4% AHI from baseline with a final AHI of less than 20 events per hour
b ODI responders achieved a minimum of 25% reduction in the 4% ODI from baseline
c Rate of revision, replacement, or explantation surgeries
d Pre-operative DISE to exclude patients with complete concentric collapse at the palate
e Based on the intention-to-treat analysis
Over the past decade, HGNS therapy has evolved from an emerging intervention to an established, evidence-based therapy within contemporary OSA management. As we continue to transition into an era of personalized medicine, a balanced understanding of each HGNS device becomes a valuable skillset for proper preoperative counseling, patient selection, and tailoring therapy to individual patient presentations. Additionally, to scale HGNS across high-volume sleep medicine practices and drive better access to care, clinicians would benefit from improved understanding of efficient yet personalized HGNS electrical programming, advanced therapy troubleshooting and optimization algorithms, and ongoing integration into the digital health platform.
Looking forward, longitudinal outcomes data and adherence monitoring will be critical components of tracking results over time and comparing mean disease alleviation among HGNS systems, as well as between HGNS and other OSA treatment modalities. Multimodality treatment approaches that combine HGNS with weight loss, positional therapy, oral appliance therapy, airway surgery, and other medical and surgical OSA interventions, also warrant further investigation. Finally, more research is needed to compare safety, objective adherence, side effects, patient preference, symptom response, and hypoxic burden and other objective metrics of disease reduction between the available systems.
Dr. Soose is a sleep medicine physician and otolaryngologist at the University of Pittsburgh, where he is the director of the sleep division and a professor in the department of otolaryngology.
Dr. Kaffenberger is a sleep medicine physician and otolaryngologist at the Pittsburgh Veterans Affairs Medical Center and the University of Pittsburgh, where he is an assistant professor in the department of otolaryngology.
Dr. Collazo is a sleep medicine fellow at the University of Pittsburgh.
This article appeared in volume 11, issue 3 of Montage magazine.
