Positive pooled analysis demonstrating the effect of dapagliflozin on albuminuria in hypertensive patients with type 2 diabetes

AstraZeneca has announced findings from a new post-hoc analysis of two Phase III trials, in which dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, 5 and 10 mg/d demonstrated greater reductions on HbA1c and systolic blood pressure (SBP) in patients with type 2 diabetes (T2DM) and hypertension compared to placebo, despite ongoing antihypertensive therapy with an ACEI or ARB, considered to be the standard of care for these patients. In this new pooled, post-hoc analysis, the effect of dapagliflozin treatment on albuminuria and estimated glomerular filtration rate (eGFR) at 12 weeks resulted in greater reductions in albuminuria compared to placebo as well as a decrease in eGFR, which was readily reversed one week after the last dose. Secondary analysis of this data also demonstrated that the effect of dapagliflozin treatment on albuminuria appears to be independent of changes in HbA1c, SBP and eGFR.¹ These results were presented at the 51st Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.

"Adult patients with hypertension and type 2 diabetes are at high risk for developing cardiovascular and renal disease, so it's imperative we investigate the effects of treatment on clinical factors that can help mitigate the risk of long-term microvascular and macrovascular complications," said lead investigator Hiddo Lambers Heerspink, Pharm.D., Ph.D., Clinical Pharmacologist in the Department of Clinical Pharmacology at the University Medical Center Groningen, the Netherlands. "We know that dapagliflozin positively affects HbA1c and blood pressure, however, in this post-hoc analysis it was also associated with greater reductions in albuminuria, and a slight but reversible decrease in eGFR. Further clinical investigations are required to establish whether these effects translate into improvements in renal outcomes."

Data were pooled from two Phase III studies in which patients with stable hypertension, various levels of baseline albuminuria and type 2 diabetes on ACEi or ARB therapy received dapagliflozin 5 mg (n=87), 10 mg (n=167) or placebo (PBO; n=189) for 12 weeks. Both doses of dapagliflozin resulted in greater percentage change from baseline in HbA1c compared to placebo (-0.5% for both dosages of dapagliflozin vs 0.01%) as well as numerically greater reduction in SBP (-12.5 and -9.8 mmHg, respectively, compared to -6.3 mmHg). Dapagliflozin is not indicated as a blood pressure lowering medication.

In this post-hoc analysis, patients receiving dapagliflozin showed greater adjusted percentage change in albuminuria from baseline, as assessed by albumin:creatinine ratio (ACR), compared to placebo (-47.4% and -45.8%, respectively, vs -18.9%).¹ Patients treated with dapagliflozin did experience numerically greater reductions in eGFR, compared to placebo (-1.5 and -3.1 mL/min/1.73m2, versus -0.3 mL/min/1.73m2, respectively); these decreases were reversible one week after treatment discontinuation.¹ This analysis noted that change in albuminuria from baseline produced by dapagliflozin was independent of the change from baseline in HbA1c, SBP and eGFR.¹ The efficacy of dapagliflozin is dependent on renal function, and is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment.

"This analysis provides new evidence evaluating the positive effects of dapagliflozin, particularly in patients with high cardiovascular and renal risk," said Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca. "These data will help inform important decisions for patients with type 2 diabetes and elevated cardiometabolic risk who may require more personalized treatment approaches."