# Effect of sleep apnoea interventions on multiple health outcomes: an umbrella review of meta-analyses of randomised controlled trials

Raoua Ben Messaoud, Camille Figard, Sébastien Baillieul, Marie

Joyeux-Faure, Marie Destors, Renaud Tamisier, Charles Khouri, Jean-Louis Pépin

► To cite this version:

Raoua Ben Messaoud, Camille Figard, Sébastien Baillieul, Marie Joyeux-Faure, Marie Destors, et al.. Effect of sleep apnoea interventions on multiple health outcomes: an umbrella review of meta-analyses of randomised controlled trials. European Respiratory Society Congress, Sep 2025, Amsterdam, Netherlands. **hal-05290753**

HAL Id: hal-05290753

https://hal.science/hal-05290753v1

Submitted on 30 Sep 2025

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# Effect of sleep apnoea interventions on multiple health outcomes: an umbrella review of meta-analyses of randomised controlled trials

Raoua Ben Messaoud, PhD¹, Camille Figard, MD², Sébastien Bailliet, MD¹,², Marie Joyeux-Faure, PharmD¹,², Marie Destors, MD,², Renaud Tamisier, MD¹,², Charles Khouri, PharmD¹,², Jean-Louis Pépin, MD¹,²

¹Univ. Grenoble Alpes, HP2 Laboratory, Inserm U1300, Grenoble, France ²EFCR Laboratory, Thorax and Vessels Division, Grenoble Alpes University Hospital, Grenoble, France ³Regional Pharmacovigilance Center & Clinical Pharmacology Unit, Grenoble Alpes University Hospital, Grenoble, France

## Introduction

### Background

Obstructive sleep apnoea (OSA) is a prevalent chronic

condition that affects 30-69 years worldwide are affected

OSA is associated with In symptoms (sleepiness, fatigue...)

and serious health comorbidities

First-line and alternative therapies:

<figure><img src="image_1.png" /></figure>

More than 6000 meta-analysis of systematic reviews and randomised controlled trials (RCTs), are available in the field of OSA treatment.

A concise summary of the best available evidence on current treatment options to help clinicians make informed decisions for implementing personalised sleep medicine

### Aim

To assimilate the vast amount of research on treatments for OSA, this umbrella review of RCT data comprehensively evaluated the impact of the main therapies and interventions for OSA management on efficacy outcomes, adherence and safety.

## Methods

### Search strategy & study selection

Blinded and collaborative manual screening for meta-analysis of RCT made by two authors*:

using Rayyan platform (http://www.rayyan.ai/)

following the specified criteria and PICO

Selection and inclusion of eligible study: one meta-analysis/intervention-outcome with the highest number of RCT or the highest quality

<figure><img src="image_2.png" /></figure>

### Keywords

<figure><img src="image_3.png" /></figure>

### Methodological quality assessment

Two reviewers independently assessed the methodological quality* using:

- the AMSTAR 2 tool

- the certainty of evidence using the GRADE framework

*Discrepancies were settled by a third author when needed

### Flowchart

<figure><img src="image_4.png" /></figure>

### Number of meta-analysis for each interventions

<figure><img src="image_5.png" /></figure>

Overlapping evidence: the same meta-analysis might assess more than one single intervention

### Population characteristics at baseline

<figure><img src="image_6.png" /></figure>

### Forest plots examples

<figure><img src="image_7.png" /></figure>

### OSA interventions on health outcomes

<figure><img src="image_8.png" /></figure>

### Conclusion

Our findings highlight the need to move beyond a one-size-fits-all approach and embrace personalised OSA management

<figure><img src="image_9.png" /></figure>

Physical activity and pharmacological innovations represent promising avenues to enhance patient-centered outcomes.

<figure><img src="image_10.png" /></figure>

This synthesis of data in this umbrella review equips clinicians and policymakers with robust evidence to optimize care pathways and improve long-term disease control in patients with OSA.

Outstanding research is needed to assess the safety, durability, and synergistic effects of combination treatments.
<figure><img src="image_11.png" /></figure>

## Devices

<figure><img src="image_12.png" /><figcaption>CPAP</figcaption></figure>

<figure><img src="image_13.png" /><figcaption>MAD</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>PT</figcaption></figure>

<figure><img src="image_15.png" /></figure>

## Surgeries

<figure><img src="image_16.png" /><figcaption>Bariatric surgery</figcaption></figure>

<figure><img src="image_17.png" /><figcaption>HNS</figcaption></figure>

<figure><img src="image_18.png" /><figcaption>Oral surgery</figcaption></figure>

<figure><img src="image_19.png" /></figure>

## Lifestyle

<figure><img src="image_20.png" /><figcaption>Physical activity</figcaption></figure>

<figure><img src="image_21.png" /><figcaption>Diet</figcaption></figure>

<figure><img src="image_22.png" /></figure>

## Drugs

<figure><img src="image_23.png" /><figcaption>Modafinil</figcaption></figure>

<figure><img src="image_24.png" /><figcaption>GLP-1</figcaption></figure>

<figure><img src="image_25.png" /><figcaption>GLP-1</figcaption></figure>

<figure><img src="image_26.png" /></figure>

*Reimbursable interventions

*Non reimbursable interventions
# Skill Development PowerPoint

P

## Population

Adult patients diagnosed with OSA and receiving the specified interventions

<figure><img src="image_27.png" /></figure>

I

## Interventions

### Active intervention
Single or Combination

<figure><img src="image_28.png" /></figure>

C

## Comparators

### Inactive control

<figure><img src="image_29.png" /></figure>

### Active intervention
Single or Combination

<figure><img src="image_30.png" /></figure>

O

## Outcomes

### AHI

<figure><img src="image_31.png" /></figure>

### ESS

<figure><img src="image_32.png" /></figure>

### BP

<figure><img src="image_33.png" /></figure>

### QoL

<figure><img src="image_34.png" /></figure>

### MACE

<figure><img src="image_35.png" /></figure>
<table><thead><tr><th>Outcome</th><th>Most Effective Interventions</th><th>Effect Size</th><th>Notes</th></tr></thead><tbody><tr><td rowspan="5">AHI</td><td>CPAP</td><td>-30.7 events/h; SMD -1.65</td><td>Strongest effect<br>Gold standard</td></tr><tr><td>Tirzepatide (GLP-1/GIP)</td><td>-21.9 events/h; SMD -0.84</td><td rowspan="3">Emerging pharmacotherapy</td></tr><tr><td>Liraglutide (GLP-1)</td><td>-6.2 events/h; SMD -0.51</td></tr><tr><td>MAD</td><td>-11.9 events/h; SMD -0.73</td></tr><tr><td>Diet</td><td>-9.8 events/h; SMD -0.63</td><td>Moderate</td></tr><tr><td rowspan="3">ESS</td><td>CPAP</td><td>-2.5; SMD -0.82</td><td>Effective</td></tr><tr><td>Stimulants</td><td>-2.7 to -4.5; SMD -0.51 to -0.88</td><td>Comparable to CPAP</td></tr><tr><td>HNS</td><td>-4.4; SMD -0.88</td><td>Strong effect</td></tr><tr><td rowspan="3">QoL</td><td>Physical activity</td><td>SMD 1.30</td><td>Largest effect</td></tr><tr><td>Stimulants</td><td>SMD 0.49-0.58</td><td>Clear benefit</td></tr><tr><td>CPAP</td><td>SMD 0.16</td><td>Small effect</td></tr><tr><td rowspan="3">BP</td><td>Tirzepatide</td><td>-7.7 mmHg; SMD -0.6</td><td>Cardiometabolic benefit</td></tr><tr><td>Oral surgery</td><td>-9.4/-6.4 mmHg</td><td>Single study</td></tr><tr><td>CPAP</td><td>-1.9 mmHg DBP</td><td>Modest</td></tr><tr><td>Adherence</td><td>MAD &lt; CPAP</td><td>No difference</td><td>Both &gt; sham</td></tr><tr><td rowspan="2">Safety</td><td>Pitolisant</td><td>No ↑ AEs</td><td>Safe</td></tr><tr><td>Modafinil / Solriamfetol</td><td>↑ AEs (SMD 0.44-0.53)</td><td>Less safe</td></tr><tr><td>GRADE<br>AMSTAR2</td><td colspan="3">Mostly low-moderate<br>Critically low to moderate</td></tr></tbody></table>
<figure><img src="image_36.png" /></figure>

## Devices

<figure><img src="image_37.png" /><figcaption>CPAP</figcaption></figure>

<figure><img src="image_38.png" /><figcaption>MAD</figcaption></figure>

<figure><img src="image_39.png" /><figcaption>PT</figcaption></figure>

<figure><img src="image_40.png" /></figure>

## Surgeries

<figure><img src="image_41.png" /><figcaption>Bariatric surgery</figcaption></figure>

<figure><img src="image_42.png" /><figcaption>HNS</figcaption></figure>

<figure><img src="image_43.png" /><figcaption>Oral surgery</figcaption></figure>

<figure><img src="image_44.png" /></figure>

## Lifestyle

<figure><img src="image_45.png" /><figcaption>Physical activity</figcaption></figure>

<figure><img src="image_46.png" /><figcaption>Diet</figcaption></figure>

<figure><img src="image_47.png" /></figure>

## Drugs

<figure><img src="image_48.png" /><figcaption>Modafinil</figcaption></figure>

<figure><img src="image_49.png" /><figcaption>GLP-1</figcaption></figure>

<figure><img src="image_50.png" /><figcaption>GLP-1</figcaption></figure>

<figure><img src="image_51.png" /></figure>
<figure><img src="image_52.png" /></figure>

<figure><img src="image_53.png" /></figure>

<figure><img src="image_54.png" /></figure>
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<figure><img src="image_62.png" /></figure>
<table><thead><tr><th>Outcome</th><th>Most Effective Interventions</th><th>Effect Size</th><th>Notes</th></tr></thead><tbody><tr><td rowspan="5">CPAP</td><td>CPAP</td><td>-30.7 events/h; SMD -1.65</td><td>Strongest effect<br>Gold standard</td></tr><tr><td>Tirzepatide (GLP-1/GIP)</td><td>-21.9 events/h; SMD -0.84</td><td>Emerging pharmacotherapy</td></tr><tr><td>Liraglutide (GLP-1)</td><td>-6.2 events/h; SMD -0.51</td><td></td></tr><tr><td>MAD</td><td>-11.9 events/h; SMD -0.73</td><td>Moderate</td></tr><tr><td>Diet</td><td>-9.8 events/h; SMD -0.63</td><td>Moderate</td></tr><tr><td rowspan="3">ESS</td><td>CPAP</td><td>-2.5; SMD -0.82</td><td>Effective</td></tr><tr><td>Stimulants</td><td>-2.7 to -4.5; SMD -0.51 to -0.88</td><td>Comparable to CPAP</td></tr><tr><td>HNS</td><td>-4.4; SMD -0.88</td><td>Strong effect</td></tr><tr><td rowspan="3">QoL</td><td>Physical activity (Stimulants)</td><td>SMD 1.30<br>SMD 0.49-0.58</td><td>Largest effect<br>Clear benefit</td></tr><tr><td>CPAP</td><td>SMD 0.16</td><td>Small effect</td></tr><tr><td>Tirzepatide<br>Oral surgery</td><td>-7.7 mmHg; SMD -0.6<br>-9.4/-6.4 mmHg</td><td>Cardiometabolic benefit<br>Single study</td></tr><tr><td>BP</td><td>CPAP</td><td>-1.9 mmHg DBP</td><td>Modest</td></tr><tr><td>Adherence</td><td>MAD = CPAP</td><td>No difference</td><td>Both > sham</td></tr><tr><td rowspan="2">Safety</td><td>Pitolisant</td><td>No ↑ AEs</td><td>Safe</td></tr><tr><td>Modafinil / Solriamfetol</td><td>↑ AEs (SMD 0.44-0.53)</td><td>Less safe</td></tr><tr><td>GRADE<br>AMSTAR2</td><td>Mostly low-moderate<br>Critically low to moderate</td><td></td><td></td></tr></tbody></table>
<figure><img src="image_63.png" /></figure>

Search
period

International prospective register of
systematic reviews

<figure><img src="image_64.png" /></figure>

PROSPERO
CRD42023420729

<figure><img src="image_65.png" /></figure>

Embose®

<figure><img src="image_66.png" /></figure>

Cochrane
Library

PubMed

<figure><img src="image_67.png" /></figure>

https://osf.io/2jysx

Registration

Keywords

P

Population

ADL patients diagnosed with
ODA and requiring the specified
interventions

<figure><img src="image_68.png" /></figure>

I

Interventions

<figure><img src="image_69.png" /></figure>

C

Comparators

<figure><img src="image_70.png" /></figure>

O

Outcomes

<figure><img src="image_71.png" /></figure>

Protocol registration

<figure><img src="image_72.png" /></figure>

PROSPERO
CRD42023420729

<figure><img src="image_73.png" /></figure>

https://osf.io/2jysx

Database search

PubMed

Clarivate
Web of Science®

<figure><img src="image_74.png" /></figure>

Embose®

<figure><img src="image_75.png" /></figure>

Cochrane
Library

<figure><img src="image_76.png" /></figure>

Search period

Continuous. Poisitive airway pressure, CPAP

Mandibular advancement, MAD

Stimulant, Wake-promoting agents, modafinil,

solifenfetol,

Pitolisant

GLP-1,

Oral surgery, maxillomandibular surgery

OMT, oropharyngeal training, myofunctional therapy

Physical activity, Exercise

Diet, caloric deficit, Weight loss, bariatric surgery

Meta-analysis, RCT

Keywords
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ENT surgery - Soft palate

<figure><img src="image_77.png" /></figure>

Costs/ year

• Often unknown

• € 400 – 10,000.

Mandibular Advancement Device

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Costs/ year

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<figure><img src="image_84.png" /></figure>

<figure><img src="image_85.png" /></figure>

1er ligne mais impact limité par la faible adhérence et la tolérance respectivement

<figure><img src="image_86.png" /></figure>

<figure><img src="image_87.png" /></figure>

Effet positif important sur la QoL, modeste sur l'IAH

Cluster 4

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<figure><img src="image_89.png" /></figure>

Supériorité de la chirurgie bariatrique sur la perte de poids mais indication limitée →Intérêt des GLP-1

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<figure><img src="image_91.png" /></figure>

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Amélioration de la QoL

Effet placebo?