Heart Failure with Preserved Ejection Fraction and Obstructive Sleep Apnea: A Novel Paradigm for Additional Cardiovascular Benefit of SGLT2 Inhibitors in Subjects With or Without Type 2 Diabetes

Adv Ther. 2022 Nov;39(11):4837-4846. doi: 10.1007/s12325-022-02310-2. Epub 2022 Sep 16.


After examining the complex interplay between heart failure (HF) in its various clinical forms, metabolic disorders like nonalcoholic fatty liver disease (NAFLD), and obstructive sleep apnea (OSA) syndrome, in this mini-review we described possible favorable effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on HF with preserved (i.e., ≥ 50%) ejection fraction (HFpEF) through enhanced cardiorenal function and visceral-subcutaneous body fat redistribution. In greater detail, on the basis of pathophysiological mechanisms underlying OSA onset and the direct positive SGLT2i effect on renal function benefiting chronic kidney disease, we emphasized the promising role of SGLT2is in prevention, rehabilitation, and treatment of patients with OSA regardless of coexisting type 2 diabetes (T2DM). Indeed, SGLT2is enhance lipolysis and fatty acid beta-oxidation. These phenomena might prevent OSA by reducing the size of visceral and subcutaneous adipose tissue and, as proven in humans and animals with T2DM, counteract NAFLD onset and progression. The aforementioned mechanisms may represent an additional SGLT2i cardioprotective effect in terms of HFpEF prevention in patients with OSA, whose NAFLD prevalence is estimated to be over 50%.

Keywords: Cardiorenal protection; Heart failure; NAFLD; Obstructive sleep apnea; Preserved ejection fraction; Rehabilitation; SGLT2is; T2DM.

Publication types

  • Editorial
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Fatty Acids / pharmacology
  • Fatty Acids / therapeutic use
  • Glucose
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Humans
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Sleep Apnea, Obstructive* / complications
  • Sleep Apnea, Obstructive* / drug therapy
  • Sodium / pharmacology
  • Sodium / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke Volume


  • Fatty Acids
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium
  • Glucose