Effects of the dual sodium–glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure

AIMS: Explore the efficacy, safety and tolerability of the dual sodium–glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type‐2 diabetes mellitus (T2DM) and heart failure. METHODS: This multicentre, parallel‐group phase IIA study randomized 125 patients with T2DM and heart failure (New York Heart Association II–IV; plasma N‐terminal pro b‐type natriuretic peptide [NT‐proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT‐proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated haemoglobin, fasting plasma glucose, weight, blood pressure, fasting lipid profile, high‐sensitivity c‐reactive protein, and safety and tolerability. RESULTS: Licogliflozin 10 mg for 12 weeks significantly reduced NT‐proBNP vs placebo (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95], P = .033). A trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 1.03], P = .064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg (−0.58 ± 0.34%) and empagliflozin (−0.44 ± 1.18%) vs placebo (−0.04 ± 0.91%). The reduction in body weight was similar with licogliflozin 50 mg (−2.15 ± 2.40 kg) and empagliflozin (−2.25 ± 1.89 kg). A numerical reduction in systolic blood pressure was seen with licogliflozin 50 mg (−9.54 ± 16.88 mmHg) and empagliflozin (−6.98 ± 15.03 mmHg) vs placebo (−2.85 ± 11.97 mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously reported. CONCLUSION: The reduction in NT‐proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure.