MUSCAT-HF: No clear evidence of cardioprotection with novel SGLT2 inhibitor in HFpEF

The novel and selective SGLT2 inhibitor luseogliflozin does not seem to produce significant reductions in B‐type natriuretic peptide (BNP) concentrations in patients with type 2 diabetes mellitus (T2DM) and heart failure with preserved ejection fraction (HFpEF) as compared with the alpha‐glucosidase inhibitor voglibose, according to data from the open‐label MUSCAT-HF trial.

In total, 169 T2DM patients with HFpEF were randomized to receive luseogliflozin 2.5 mg once daily (n=86) or voglibose 0.2 mg three times daily (n=85) for 12 weeks. Expansion of follow‐up for an additional 12 weeks was continued in patients who agreed.

Three patients did not receive any doses of a study drug and were excluded from all analyses. The safety population included 166 patients, while the efficacy analysis included 165 patients, 83 in the luseogliflozin (mean age, 71.7 years; 66 percent male) and 82 in the voglibose (mean age, 74.6 years; 59 percent male) groups. BNP was used as the index of the therapeutic effect.

The mean systolic blood pressure and heart rate were similar in the luseogliflozin and voglibose groups. At baseline, the median BNP concentration was 63.7 vs 75.1 pg/mL, respectively, and the median NT‐proBNP concentration was 203 vs 200 pg/mL, respectively.

BNP concentrations decreased over time in the luseogliflozin group. At week 12, the change from baseline was –9.0 percent, which was not significantly different compared with voglibose (−1.9 percent; ratio of change, 0.93, 95 percent confidence interval, 0.78–1.10; p=0.26).

Results for safety outcomes followed a similar pattern. All adverse events and exploratory haemodynamic outcomes were similar between the two groups, except for a significantly lower rate of gastrointestinal symptoms (p=0.013) and greater reduction in systolic blood pressure (p=0.036) with luseogliflozin.