The Effects of Canagliflozin compared to Sitagliptin on Cardiorespiratory Fitness in Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: Results of the CANA-HF Study.

BACKGROUND: Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness (CRF) and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. METHODS: We conducted a double blinded randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) slope (co-primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2 , ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12-week follow-up. RESULTS: The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the 2 groups (P = 0.083 and P = 0.98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL•kgLM-1 •min-1 , P = 0.036), VAT (+1.5 mL•kg-1 •min-1 , P = 0.012), and VO2 matched for respiratory exchange ratio (+2.4 mL•Kg-1 •min-1 , P = 0.002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (-12.1, P = 0.018). CONCLUSIONS: In this small and short-term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favorable trends observed on several additional surrogate endpoints such as lean peak VO2 , VAT and quality of life. This article is protected by copyright. All rights reserved.