Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream?

Sleep. 2023 Oct 11;46(10):zsad224. doi: 10.1093/sleep/zsad224.

Abstract

Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.

Keywords: OSA; OSA - endocrine morbidity/interactions; OSA - pharmacotherapy; endocrinology; incretins; obesity; weight loss; weight management.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Incretins / physiology
  • Incretins / therapeutic use
  • Obesity / complications
  • Obesity / drug therapy
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / drug therapy
  • Weight Loss

Substances

  • Incretins