Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension.

Tikkanen I, Narko K, Zeller C, et al. on behalf of the EMPA-REG BP Investigators
Diabetes Care. 2014 Sep 30. pii: DC_141096. [Epub ahead of print]

Background

Patients with diabetes have a high lifetime risk of cardiovascular disease (CVD), thus management of these patients should not only focus on control of glycaemia but also address CV risk factors. About two thirds of patients with diabetes have hypertension [1,2]. Lowering blood pressure (BP) in patients with diabetes can reduce CV events and has a renoprotective effect [3-5]. The updated Joint National Committee (JNC) guidelines recommend a target BP < 140/90 mmHg in patients with diabetes and hypertension [6]. Combination therapy is often required, since BP control is difficult to achieve in these patients [7].
Empagliflozin is a potent and selective sodium glucose cotransporter 2 (SGLT2) inhibitor, in development for treatment of type 2 diabetes (T2DM). Inhibition of SGLT2 leads to increased urinary glucose excretion and improved hyperglycaemia, without affecting β-cell function and insulin resistance [8].
EMPA-REG BP is a phase III study to determine the effect of 10 mg and 25 mg empagliflozin o.d. for 12 weeks on BP, glycaemic control and to assess safety and tolerability, as compared with placebo, in patients with T2DM and hypertension.

Main results

• Significantly larger mean 24-h SBP and DBP reductions were seen in week 12 with empagliflozin 10 mg (-3.44 mmHg and -1.36 mmHg for SBP and DBP) and 25 mg (-4.16 mmHg and -1.72 mmHg for SBP and DBP) than with placebo. Patients with 24-h mean ABPM >130/80 mmHg at baseline showed greater decreases at 12 week than those with BP<130/80 mmHg.
• Changes in night-time BP were less pronounced than daytime effects of empagliflozin as compared to placebo.
• BP lowering was not associated with increases in pulse rate (mean change from baseline in mean 24-h pulse rate: -0.27 (SD: 6.10) bpm with placebo, and -0.17 (SD: 7.70) bpm and -0.74 (SD: 6.16) bpm with empagliflozin 10 mg and 25 mg respectively.
• Empagliflozin 10 mg and 25 mg showed significantly greater reductions in HBA1c (-0.62% and -0.65% vs. placebo for empagliflozin 10mg and 25mg) and FPG from baseline, as well as significantly greater reductions in body weight (-1.49 and -1.98 vs. placebo for 10mg and 25 mg respectively).
• Adverse effects (AEs) reported were generally mild or moderate. More patients on placebo reported serious AEs; one serious event was considered drug-related (sudden death in a patient receiving 10 mg empagliflozin). The most frequently reported drug-related AEs were pollakiuria, hypoglycaemia, polyuria and thirst.

Conclusion

These phase III data show that treatment with empagliflozin 10 mg or 25 mg for 12 weeks gave a clinically meaningful improvement in 24-h SBP and DBP, as compared with placebo, in patients with T2DM and hypertension. HbA1c and body weight were also significantly reduced. Control of BP and glycaemia has previously been shown to reduce the risk of CV complications and mortality in patients with T2DM and hypertension. The ongoing EMPA-REG OUTCOME trial will determine the CV safety and possible benefits on CV and microvascular outcomes of empagliflozin in patients with T2DM at high CV risk.

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