Comment on Neeland et al. The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care 2020;43:3007–3015

Insuline use could increase the risk of obstructive sleep apnea in type 2 diabetes mellitus

“…Currently, however, there is a number of new medications to control T2DM. Many of these medications, such as GLP1 analogues and SGLT2 inhibitors, associate with weight and body fat reductions 18 .Previous studies have shown that both medications have benefits in terms of weight and OSA in these patients 19,20 .Despite the financial burden that such treatments impose, choosing these drugs instead of insulin might be cost-effective for selected groups of patients: obese subjects, patients already with OSA and those with a high risk score for OSA. Costeffectiveness would be obtained by the interruption of the insulin-OSA-insulin cycle.…”

Response to Comment on Neeland et al. The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care 2020;43:3007–3015

“…We acknowledge the thought-provoking hypothesis that Brikman and Dori ( 1 ) suggest to explain the lower incidence of new-onset obstructive sleep apnea (OSA) observed among participants treated with empagliflozin compared with placebo we recently reported. They suggest that sodium–glucose cotransporter 2 inhibition (SGLT2i) decreases endogenous carbon dioxide (CO 2 ) through a shift in metabolic substrate away from carbohydrates and toward utilization of lipids and proteins, leading to a lower concentration of CO 2 in the pulmonary circulation and lower likelihood of apneic events during sleep.…”

GLP-1 receptor agonists, SGLT-2 inhibitors, and obstructive sleep apnoea: can new allies face an old enemy?

“…In this way, SGLT2 inhibitors may decrease rostral-to-caudal fluid shifts in the recumbent sleep position, cardiac preload, and intrathoracic fluid retention; (iii) due to the modest increase in urinary frequency, manifested usually as nocturia, SGLT2 inhibitors could promote interrupted sleep cycles and suppress the duration of REM sleep (a higher risk period for OSA events); (iv) SGLT2 inhibitors can suppress circadian sympathetic nervous system activation and its related conditions (such as non-dipping pattern of hypertension, cardiac autonomic neuropathy, and stroke); (v) forced glucosuria after their administration can reduce the availability of glucose as an energy fuel. In this way other substrates are utilized, and less endogenous CO 2 production is expected, with less CO 2 to be removed by the respiratory tract; and (vi) modulation of arousal threshold, muscle compensation, and loop gain [78,[93][94][95][96][97][98].…”