The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The <scp>CANA‐HF</scp> study
Salvatore Carbone, Hayley Billingsley, Justin M. Canada, Edoardo Bressi, Brando Rotelli, Dinesh Kadariya, Dave L. Dixon, Roshanak Markley, Cory R. Trankle, Richard H. Cooke, Krishnasree Rao, Keyur B. Shah, Horacio Medina de Chazal, Juan Guido Chiabrando, Alessandra Vecchié, Megan Dell, Virginia Mihalick, Roberta C. Bogaev, Linda L. Hart, Benjamín Van Tassell, Ross Arena, Francesco S. Celi, Antonio Abbate
Abstract
Abstract Background Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. Methods We conducted a double‐blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO 2 ) and minute ventilation/carbon dioxide production (VE/VCO 2 ) slope (co‐primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO 2 , 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 VO 2 and VE/VCO 2 slope between the two groups ( P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO 2 (+2.4 mL kg LM −1 min −1 , P = .036), VAT (+1.5 mL kg −1 min −1 , P = .012) and VO 2 matched for respiratory exchange ratio (+2.4 mL Kg −1 min −1 , P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (−12.1, P = .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 VO 2 or VE/VCO 2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO 2 , VAT and quality of life.