Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes

Abstract

Abstract. Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81 yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP) and apnea hypopnea index (AHI) were evaluated before and after SGLT2i administration. The relationships between the reduction in AHI and the other variables were examined using Pearson correlation analysis. We have got result that SGLT2i reduced AHI from 31.9 ± 18.0 to 18.8 ± 11.5 events per hr (p = 0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The Pearson correlation analysis showed a significant relationship between the reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.Key words: Sodium glucose cotransporter 2 inhibitors, Obstructive sleep apnea syndrome, Type 2 diabetes THE OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) is a common and under-diagnosed disorder, associated with multiple comorbidities including obesity, metabolic syndrome, dyslipidemia and diabetes. OSAS contributes to an increased risk of cardiovascular mortality, a reduced quality of life, and is a major factor in some motor vehicle accidents by causing sleepiness of the driver [1][2][3][4]. Excess weight is considered to be the most important risk factor for OSAS [5,6] as it has been shown that between 60-70% of people with the synSubmitted Oct. 29, 2017; Accepted Jan. 11, 2018 as EJ17-0440 Released online in J-STAGE as advance publication Feb. 20, 2018 Correspondence to: Takashi Yoneda M.D., Ph.D., Kanazawa University, Takaramachi 13-1, Kanazawa, Ishikawa 920-8641, Japan. E-mail: endocrin@med.kanazawa-u.ac.jp *Equally contributing author: Shigehiro Karashima M.D., Ph.D. drome are either overweight or obese [7,8]. Furthermore, the prevalence of OSAS in obese patients with type 2 diabetes was reported to be 86% [9]. This indicates there is a close link between OSAS and type 2 diabetes and impaired glycemic control.Sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce plasma glucose levels in patients with type 2 diabetes by decreasing renal glucose reabsorption and increasing urinary glucose excretion [10]. Diuresis and calorie loss induced by SGLT2i results in reductions in body weight (BW) and blood pressure (BP), leading to improved insulin sensitivity and reduced arterial stiffness, respectively. As a consequence, SGLT2is would be expected to have pleiotropic effects in patients with type 2 diabetes, including reduced BW and severity of hypertension...

Basic and Clinical Pharmaco-Therapeutics of SGLT2 Inhibitors: A Contemporary Update

“…improved insulin sensitivity) remain pleiotropic effects of SGLT2 inhibitors, but not primary indicative benefits. Other conditions associated with increased weight, including polycystic ovarian disease or obstructive sleep apnoea, may also benefit from SGLT2 inhibitors in certain patients [57,59,60]. The present evidence, although limited in several aspects, does suggest clinically meaningful propositions of SGLT2 inhibitors that are worthy of further evaluation.…”

Empagliflozin therapy and insulin resistance-associated disorders: effects and promises beyond a diabetic state

“…SGLT2 inhibitors can improve several metabolic factors related to OSAS, and their possible role is under investigation [15,17,18]. Preliminary results of their administration in patients with OSAS and T2D suggested not only important metabolic benefits but also significant improvements in apnoea hypopnoea index (AHI), hypoxaemia during sleep, and excessive daytime sleepiness [132,133]. A recent exploratory post-hoc analysis of the EMPA-REG OUTCOME trial suggested that approximately 6% of participants had OSAS at baseline, and that patients with OSAS experienced higher overall all-cause mortality, as well as cardiovascular and kidney events, confirming the huge cardiorenal burden that characterize this population [134,135].…”

A Response To: Sodium–Glucose Cotransporter 2 Inhibitors and Major COVID-19 Outcomes: Promising Mechanisms, Conflicting Data, and Intriguing Clinical Decisions

“…It should be of interest to emphasize some more activities exerted by the drugs of this class on respiratory function. For instance, patients suffering from obstructive sleep apnea syndrome (OSAS) may benefit from the weight loss obtained with SGLT2-i [8]. Furthermore, empagliflozin was able to lower mortality in experimental pulmonary hypertension.…”