English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Aims  Dapagliflozin is a sodium–glucose co‐transporter 2 inhibitor that has been developed as oral glucose lowering drug. The original dosefinding studies focused on optimal glycaemic effects. However, dapagliflozin also affects various cardiorenal risk markers and provides cardiorenal protection. To evaluate whether the currently registered doses of 5 and 10 mg are optimal for cardiorenal efficacy and safety, we characterized the relationship between dapagliflozin exposure and nonglycaemic cardiorenal risk markers as well as adverse events.    Methods  Data were obtained from a pooled database of 13 24‐week randomized controlled clinical trials of the clinical development programme of dapagliflozin. The exposure–response relationship was quantified using population pharmacodynamic and repeated time‐to‐event models.    Results  A dose of 10 mg dapagliflozin resulted in an average individual exposure of 638 ng h/mL (95% prediction interval [PI]: 354–1061 ng h/mL), which translated to 71.2% (95% PI: 57.9–80.5%), 61.1% (95% PI: 58.0–64.8%), 91.3% (95% PI: 85.4–94.6%) and 25.7% (95% PI: 23.5–28.3%) of its estimated maximum effect for fasting plasma glucose, haematocrit, serum creatinine and urinary albumin–creatinine ratio, respectively.    Conclusion  We demonstrate that doses higher than 10 mg could provide additional beneficial effects in haematocrit, systolic blood pressure, urinary albumin–creatinine ratio and uric acid, without obvious increases in the rate of adverse events. These results raise the question whether future outcome studies assessing the benefits of higher than currently registered dapagliflozin doses are merited.

Exposure–response relationships of dapagliflozin on cardiorenal risk markers and adverse events: A pooled analysis of 13 phase II/III trials