Abstract

Hypertension (HTN) in Type 2 diabetes (T2D) is often treated with an ACEi/ARB + additional antihypertensives agents (AHTs). Dapagliflozin (DAPA) is an inhibitor of sodium glucose co-transporter 2, reducing hyperglycemia in T2D by increasing urinary glucose excretion. This is associated with weight reduction, osmotic diuresis and serum uric acid reduction, all of which may contribute to BP lowering. This Phase 3 study assessed 12 weeks of DAPA 10 mg (N=225) or placebo (PBO; N=224) in T2D patients (HbA1c 7.0-10.5%) with HTN (seated SBP / DBP 140 - <165 / 85 - <105 mmHg) receiving glucose-lowering drugs, an ACEi/ARB, + an additional AHT: β-blockers (27%), Ca-channel blockers (CCBs; 27%), thiazide/thiazide-like diuretics (diuretics; 44%) or α-adrenergic antagonists (α-AAs; 1%). Main results were presented previously. Here we describe treatment effects according to the additional AHT (α-AA group not analyzed due to small sample size). Patients were randomized to DAPA 10 mg or PBO, stratified by insulin use and diuretics vs CCBs/β-blockers/α-AA. Baseline characteristics were similar for DAPA vs PBO. Reduction in HbA1c and mean 24-hour ambulatory SBP was greater with DAPA vs PBO overall, and appeared greater with DAPA vs PBO in all AHT sub-groups (Fig). Reduction in seated SBP was greater with DAPA overall (diff vs PBO; –4.28 [95% CI: –6.54, –2.02] mmHg) and also appeared greater with DAPA in sub-groups (diff vs PBO: β-blockers –5.76 [–10.28, –1.23]; CCB –5.13 [–9.47, –0.79]; diuretics –2.38 [–6.16, 1.40] mmHg). Serum uric acid decreased more with DAPA overall (diff vs PBO; –0.40 [95% CI: –0.57, –0.23]), and was observed to decrease more with DAPA in sub-groups (diff vs PBO: β-blockers –0.62 [–0.95, –0.29]; CCBs –0.33 [–0.65, –0.01]; diuretics –0.22 [–0.49, 0.05] mg/dL). DAPA was well tolerated; AEs were similar for DAPA (44%) vs PBO (42%). In summary, regardless of the concomitant AHT, DAPA reduced HbA1c, SBP and serum uric acid vs PBO in patients with uncontrolled T2D and HTN.

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