The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial

Abstract

OBJECTIVE To explore the effects of empagliflozin on the incidence of obstructive sleep apnea (OSA) and its effects on metabolic, cardiovascular (CV), and renal outcomes among participants with or without OSA in the EMPA-REG OUTCOME trial. RESEARCH DESIGN AND METHODS Participants with diabetes and CV disease were randomized to empagliflozin (10 and 25 mg) or placebo daily in addition to standard of care. OSA was assessed by investigator report using Medical Dictionary for Regulatory Activities version 18.0, and CV outcomes were independently adjudicated. Analyses were performed using multivariable-adjusted Cox regression models. RESULTS OSA was reported in 391 of 7,020 (5.6%) participants at baseline. Those with OSA were more likely to be male (83% vs. 71%) and to have moderate to severe obesity (BMI ≥35 kg/m2; 55% vs. 18%). Over a median of 3.1 years, empagliflozin had similar placebo-adjusted reductions in HbA1c, waist circumference, and systolic blood pressure, regardless of OSA status, but a larger effect on weight (adjusted mean ± SE difference at week 52: OSA vs. no OSA −2.9 ± 0.5 vs. −1.9 ± 0.1 kg). Incidence of 3-point major adverse CV events, CV death, heart failure hospitalization, and incident or worsening nephropathy in the placebo group was 1.2- to 2.0-fold higher for those with baseline OSA compared with those without. Empagliflozin significantly reduced the risk for outcomes regardless of OSA status (P-interaction all >0.05). Fifty patients reported a new diagnosis of OSA through 7 days after medication discontinuation, and this occurred less often with empagliflozin treatment (hazard ratio 0.48 [95% CI 0.27, 0.83]). CONCLUSIONS In EMPA-REG OUTCOME, participants with OSA had greater comorbidity and higher frequency of CV and renal events. Empagliflozin had favorable effects on risk factors and CV and renal outcomes regardless of preexisting OSA and may also reduce the risk for new-onset OSA.

Possible Preventative/Rehabilitative Role of Gliflozins in OSA and T2DM. A Systematic Literature Review-Based Hypothesis

“…Moreover, empagliflozin proved beneficial for cardiovascular and renal outcomes regardless of OSA but could also reduce the risk for OSA [196] by counteracting the hyperproduction and the hyperactivity of leptin [197], whose levels are elevated in OSA patients [65]. The latter hypothesis is still controversial [198].…”

Efficacy of empagliflozin for weight and glycemic control of a patient with Prader-Willi syndrome, systemic lymphedema and extreme obesity: a case report

“…Noteworthy, the absolute body weight of our patient before empagliflozin therapy was 136 kg, much greater than those observed in similar case reports with PWS patients [ 3 , 9 ]. In this regard, empagliflozin presents protector role against cardiovascular and renal events [ 10 ].…”

Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update

“…Liraglutide 3 mg was studied in non-diabetic obese patients suffering from moderate or severe OSA, in the absence of positive airway pressure (PAP) therapy, and a significant reduction in weight and AHI was observed after 32 weeks of treatment, with a trend toward improved oxygen saturation, sleep architecture, and sleep/health-related QoL outcomes ( 114 ). Among SGLT2 inhibitors, empagliflozin has beneficial effects on cardiovascular and renal outcomes in type 2 diabetic patients and may reduce the risk of new-onset OSA ( 115 ), possibly mediated by weight loss and the diuretic/natriuretic action of the drug ( 115 ). It may, therefore, be attractive in diabetic patients with CP unless fluid and electrolytic imbalance is present, although experience is still lacking.…”