Temporal changes in obstructive sleep apnea severity and body composition parameters during 6-month tofogliflozin administration in patients with heart failure and type 2 diabetes mellitus: a TOPARDS-HF substudy

PURPOSE: Obstructive sleep apnea (OSA) is closely associated with obesity and fluid retention. Our previous study suggested that, in patients with heart failure, the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, promotes diuresis and weight loss and improves OSA severity. However, whether changes in the apnea-hypopnea index (AHI) are chronologically associated with body composition parameters remains unclear. METHODS: We enrolled 10 patients (six men) with OSA. They received tofogliflozin (20 mg) daily for 6 months. The AHI was assessed using WatchPAT® at baseline, 3, and 6 months. Body composition, including water content and fat mass, was also measured. AHI changes measured using the WatchPAT peripheral arterial tonometry-derived AHI (pAHI) and their correlations with changes in body composition parameters were analyzed. RESULTS: Tofogliflozin administration significantly reduced pAHIs at 3 and 6 months compared to baseline, but more at 3 months, whereas body weight and body water content decreased over time. The %Δbody water content did not correlate with %ΔpAHI at 3 months (r = 0.47, p = 0.139), but there was a significant correlation at 6 months (r = 0.57, p = 0.047). The %Δbody weight and %Δfat mass reduction were significantly associated with improvement in %ΔpAHI at 3 months (r = 0.65, p = 0.042 and r = 0.66, p = 0.044, respectively), but no correlations were observed at 6 months. CONCLUSIONS: Tofogliflozin significantly improved OSA severity at 3 and 6 months; however, more improvements were observed at 3 months. These improvements were accompanied by gradual reductions in body water content, especially from baseline to 6 months. In contrast, body weight and fat mass reduction impacted the OSA severity in the early stages.