Dapagliflozin ‘could aid hypertension’
New research has outlined the “positive effects” of dapagliflozin with people with type 2 diabetes with high cardiovascular and renal risk.
Two Phase III clinical trials have demonstrated the safety and efficacy of dapagliflozin 5mg and 10mg when added to standard of care in patients with hypertension and type 2 diabetes.
The findings from the post-hoc analysis by AstraZeneca have shown dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, 5and 10mg/d delivered greater reductions on HbA1c and systolic blood pressure (SBP) in patients with type 2 diabetes and hypertension compared to placebo.
This was despite ongoing antihypertensive therapy with an ACEI or ARB, which is considered to be the standard of care for the people with those conditions.
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 estimated glomerular filtration rate (eGFR), which was readily reversed one week after the last dose.
This post-hoc analysis indicates it is also associated with greater reductions in albuminuria
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.
The results were presented at the 51st Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.
Lead investigator Hiddo Lambers Heerspink, Pharm.D., PhD, Clinical Pharmacologist in the Department of Clinical Pharmacology at the University Medical Center Groningen in the Netherlands, said: “Patients with hypertension and type 2 diabetes are at greater 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.
“We know that dapagliflozin positively effects HbA1c and blood pressure, however this post-hoc analysis indicates it is also associated with greater reductions in albuminuria, despite a slight but reversible decrease in eGFR, which warrants further clinical investigation as we seek to establish the relationship between markers of nephropathy with improvements in renal function.”
The data was 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=85), 10 mg (n=165) or placebo (PBO; n=185) for 12 weeks.
Both doses of dapagliflozin resulted in greater adjusted percentage change from baseline compared to placebo in HbA1c (-0.5 per cent for both dosages vs 0.01 per cent; [95 per cent CI]) as well as in SBP (-12.5 and -9.8 mmHg, respectively, compared to -6.3 mmHg; [95 per cent CI]).
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 (-47.4per cent and -45.8 per cent, respectively, vs -18.9 per cent; [95 per cent CI]).
Patients treated with dapagliflozin did experience greater reductions in eGFR, compared to placebo (-1.5 per cent and -3.1 per cent mL/min/1.73m2, respectively, versus -0.3 per cent mL/min/1.73m2; [95 per cent CI]); however, these decreases reversed one week after the last dose of treatment (0.9 per cent and 0.7 per cent mL/min/1.73m2, respectively, vs -0.9 per cent mL/min/1.73m2).
Secondary analysis on the effects on albuminuria was repeated with adjustments in HbA1c, SBP and eGFR from the original two Phase III studies and the ACR-reducing effect appears to be independent of the changes in HbA1c and systolic blood pressure, two cardiovascular and renal risk markers.
Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development at AstraZeneca, said: “This analysis provides important new evidence demonstrating the positive effects of dapagliflozin, particularly in patients with high cardiovascular and renal risk.”
“These data will help inform important decisions for patients with type 2 diabetes and elevated cardiometabolic risk who may require more personalised treatment approaches.”