What’s new in sleep medicine (2024–2025): therapies, diagnostics, and prodromal biomarkers

Below is a clinician-focused synthesis of the most consequential recent developments in sleep medicine, with primary literature for follow-up.

1) Pharmacotherapy for obstructive sleep apnoea (OSA)

• GLP-1/GIP agonist for OSA: Two phase-3 RCTs showed tirzepatide reduced AHI over 52 weeks in adults with moderate–severe OSA (with or without CPAP); this underpinned U.S. approval in 2024/25 and positions anti-obesity pharmacotherapy as disease-modifying for OSA in patients with obesity. Consider for CPAP-intolerant patients and as an adjunct to device/surgical care. New England Journal of Medicine+1

Clinical take: Expect greatest benefit when weight loss is etiologic; airway anatomy–driven OSA will still need PAP, OA, positional therapy, or surgery.

2) Device therapies: upper-airway and ventilatory pacing

• Hypoglossal nerve stimulation (HGNS): Contemporary cohorts and reviews reinforce HGNS efficacy and adherence in appropriately selected OSA (BMI limits, CCC > 25%, palatal collapse phenotype). Longitudinal programme-use data highlight predictors of adherence—useful for patient selection and counselling. ScienceDirect+2PMC+2
• Phrenic nerve stimulation (TPNS) for central sleep apnoea: Updated observational data and narrative syntheses show 1-year improvements in AHI/CAI and sleepiness after transvenous phrenic pacing in moderate–severe CSA, including heart-failure populations. Consider when PAP fails or is not tolerated. PubMed+1

Clinical take: Phenotype your patient (OSA vs CSA, collapsibility, BMI, HF status) to triage to HGNS/TPNS vs PAP-based strategies.

3) Narcolepsy and hypersomnolence: orexin-2 receptor (OX2R) agonists

• Oral OX2R agonists: Phase-2 data for TAK-861 and oveporexton (formerly TAK-??? in some reports) show clinically meaningful improvements in wakefulness and cataplexy in narcolepsy type 1. Safety and liver-signal monitoring remain central given the class experience. American Academy of Neurology+1
• Intravenous danavorexton (TAK-925): Proof-of-concept trials continue to demonstrate robust wake promotion; ancillary work suggests reversal of opioid-induced respiratory depression without blunting analgesia—mechanistically relevant for peri-operative sedation and sleep-disordered breathing research. Oral long-acting successors are in development. PubMed+2PubMed+2

Clinical take: These agents target the core pathobiology of narcolepsy (orexin deficiency) and may reshape first-line therapy once oral options are approved.

4) Insomnia: dual-orexin receptor antagonists (DORAs) and digital CBT-I

• DORAs (daridorexant): New comparative meta-analysis and safety updates support efficacy on sleep initiation/maintenance and next-day functioning, with low risk of tolerance/withdrawal—useful in patients at risk from GABAergic hypnotics. PMC+1
• Scalable CBT-I: RCTs and a 2025 meta-analysis show fully automated/digital CBT-I confers clinically meaningful improvements across diverse populations (e.g., cancer survivors, veterans with mTBI), supporting stepped-care models where therapist access is limited. JAMA Network+2JAMA Network+2

Clinical take: Start with CBT-I (digital or therapist-led); consider DORA when pharmacotherapy is warranted, especially where residual daytime functioning is a concern.

5) Diagnostics: home testing, wearables, and beyond-PSG monitoring

• Home sleep testing: Recent position statements and reviews endorse HSAT and emerging home-PSG pathways for suitable OSA phenotypes; multi-night testing reduces night-to-night variability errors. Paediatric evidence (e.g., WatchPAT) is accruing but still narrower than adult data. ScienceDirect+3PMC+3SpringerLink+3
• Wearables for sleep staging: Validation work shows improving agreement for summary metrics (TST, WASO) in some devices (e.g., Oura) but persistent limitations for stage-level concordance; use as adjuncts, not PSG replacements, in clinical decision-making. PMC+2ScienceDirect+2

Clinical take: Use HSAT within guideline indications; reserve PSG for non-diagnostic HSAT, suspected CSA, PLMD, parasomnias, or complex comorbidity.

6) REM sleep behaviour disorder (RBD) as a prodromal window to synucleinopathy

• Conversion risk and subtyping: Contemporary reviews reaffirm high long-term phenoconversion rates from idiopathic RBD (iRBD) to α-synucleinopathies, and propose imaging- and clinical-feature-based biotypes to stratify risk and trial readiness. BioMed Central+2Nature+2
• Pathology-specific biomarkers: Multicentre studies report high sensitivity/specificity for cutaneous phosphorylated α-synuclein by skin biopsy in established synucleinopathies; seed-amplification assays (RT-QuIC/SAAs) in CSF and skin are advancing toward same-day workflows and show strong CSF–skin concordance. Early iRBD cohorts suggest substantial positivity rates, supporting enrichment strategies for disease-modifying trials. PMC+3JAMA Network+3Nature+3
• Home/low-burden detection: Systematic reviews catalogue novel home-based tools to screen for RBD where vPSG access is limited—potentially widening prodromal case finding. Nature

Clinical take: For suspected iRBD, consider counselling about neurodegenerative risk, safety measures, and clinical-trial referral. Biomarker testing (skin SAA/α-syn, CSF SAA) is emerging as a research-enabled option and may soon influence routine risk stratification.

Practical implications for clinics in 2025

1. Individualise OSA care: Combine weight-centric pharmacotherapy (tirzepatide) with anatomical therapies (PAP, OA, HGNS). Screen for CSA and consider phrenic pacing where appropriate. New England Journal of Medicine+2ScienceDirect+2
2. Prepare for orexin restoration: Track OX2R agonist programmes; anticipate integration alongside (or before) traditional wake-promoting agents in NT1. American Academy of Neurology
3. Modernise insomnia pathways: Implement stepped-care with dCBT-I at scale; reserve DORAs for pharmacologic indications, favouring their safety profile. Nature+1
4. Adopt judicious remote diagnostics: Use HSAT and validated wearables to extend reach while recognising limits vs PSG, especially for staging and non-OSA disorders. PMC+1
5. Treat iRBD as a prodrome: Standardise safety counselling, assess comorbid sleep pathology, and engage with biomarker-based research networks for early neuroprotective trials. JAMA Network

Selected references (peer-reviewed)

• Malhotra A, et al. Tirzepatide for the treatment of OSA—two phase-3 RCTs. N Engl J Med. 2024. New England Journal of Medicine
• Anderer S. FDA approves tirzepatide for OSA—context and details. JAMA. 2025. JAMA Network
• Alrubasy WA, et al. Hypoglossal nerve stimulation for OSA—review. Sleep Med Rev. 2024. ScienceDirect
• Mease J, et al. Phrenic nerve stimulation for CSA—1-year outcomes. Sleep Breath. 2024. PubMed
• Bekfani T, et al. Revisiting TPNS in CSA—narrative review. J Clin Med. 2025. PMC
• TAK-861 phase-2 in NT1. Neurology. 2025. American Academy of Neurology
• Dauvilliers Y, et al. Oveporexton (OX2R agonist) phase-2 in NT1. Sleep Med. 2025. PubMed
• Evans R, et al. Danavorexton (TAK-925) wake promotion (human & translational). J Clin Sleep Med. / Br J Anaesth. 2023–2025. PubMed+1
• Kishi T, et al. Comparative efficacy/safety of daridorexant vs other hypnotics—systematic review/meta-analysis. Neurosci Biobehav Rev. 2025. PMC
• Wang Q, et al. Daridorexant safety update. J Affect Disord. 2024. ScienceDirect
• Hwang JW, et al. Fully automated digital CBT-I—systematic review/meta-analysis (29 RCTs). NPJ Digit Med. 2025. Nature
• Starling CM, et al.; Malarkey ME, et al. dCBT-I RCTs in cancer survivors; veterans with mTBI. JAMA Netw Open. 2024. JAMA Network+1
• Robbins R, et al.; Svensson T, et al. Wearable validation vs PSG (Oura/Apple/Fitbit). Sleep Health 2024; Sleep Med 2024. PMC+1
• Gibbons CH, et al. Skin biopsy detection of phosphorylated α-synuclein in synucleinopathies (multicentre). JAMA. 2024. JAMA Network
• Parveen S, et al. Same-day α-syn RT-QuIC SAA—methodological advance. Communications Medicine. 2025. Nature
• Bsoul R, et al. Accurate α-syn SAA in CSF & skin; high CSF–skin agreement. Acta Neuropathol Commun. 2025. BioMed Central
• Stefani A, et al. Synopsis of iRBD as early α-synucleinopathy; conversion risk and biomarkers. Mol Neurodegener. 2025. BioMed Central