Dapagliflozin >10 mg provides added benefits in haematocrit, SBP, albuminuria, uric acid

Dapagliflozin therapy with doses higher than 10 mg appears to deliver greater beneficial effects in haematocrit, systolic blood pressure, urinary albumin–creatinine ratio, and uric acid, with no evident increases in the rate of adverse events, a recent study has shown.

A 10-mg dose of dapagliflozin led to an average individual exposure of 638 ng h/mL (95 percent prediction interval [PI], 354–1,061). This translated to 71.2 percent (95 percent PI, 57.9–80.75) of its estimated maximum effect for fasting plasma glucose, 61.1 percent (95 percent PI, 58.0–64.8 percent) for haematocrit, 91.3 percent (95 percent PI, 85.4–94.6 percent) for serum creatinine, and 25.7 percent (95 percent PI, 23.5–28.3) for urinary albumin–creatinine ratio.

“These results raise the question whether future outcome studies assessing the benefits of higher than currently registered dapagliflozin doses are merited,” the investigators said.

This study sought to determine whether the currently registered doses of 5 and 10 mg were optimal for cardiorenal efficacy and safety by describing the relationship between dapagliflozin exposure and nonglycaemic cardiorenal risk markers as well as adverse events.

The investigators collected data from a pooled database of 13 24-week randomized controlled clinical trials of the clinical development programme of dapagliflozin. Population pharmacodynamic and repeated time-to-event models were used to quantify the exposure–response relationship.

“Dapagliflozin is a sodium–glucose co‐transporter 2 inhibitor that has been developed as oral glucose-lowering drug. The original dose-finding studies focused on optimal glycaemic effects. However, dapagliflozin also affects various cardiorenal risk markers and provides cardiorenal protection,” the investigators explained.