Blood pressure‐lowering effect of the sodium glucose co‐transporter‐2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension

Abstract

This study compared the blood pressure-lowering effect of ertugliflozin (1, 5, 25 mg), hydrochlorothiazide (HCTZ; 12.5 mg) and placebo in 194 patients with type 2 diabetes mellitus and hypertension for 4 weeks using ambulatory blood pressure monitoring. Endpoints (change from baseline to week 4) were: 24-h mean systolic blood pressure (SBP; primary); daytime, night-time, seated predose SBP, 24-h, daytime, night-time, seated predose diastolic blood pressure, 24-h urinary glucose excretion and fasting plasma glucose (FPG; secondary). Safety and tolerability were monitored. Significant decreases in placebo-corrected 24-h mean SBP (-3.0 to -4.0 mmHg) were recorded for all doses of ertugliflozin (for HCTZ, this was -3.2 mmHg). Daytime, but not night-time SBP was consistently reduced. Ertugliflozin produced dose-dependent significant decreases in FPG and increases in urinary glucose excretion. No notable changes in plasma renin activity or urinary aldosterone were seen. The most common adverse events were urinary tract infection, genital fungal infection, upper respiratory tract infection and musculoskeletal pain.

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

“…This effect has been confirmed with all SGLT2 inhibitors [29,40] : canagliflozin [41,42], dapagliflozin [43][44][45], empagliflozin [46], ertugliflozin [47] (Table 1). Generally, the reduction in systolic BP was greater (at least twofold) than the reduction in diastolic BP.…”

“…Generally, the reduction in systolic BP was greater (at least twofold) than the reduction in diastolic BP. The BP reduction has been demonstrated when BP was controlled in seated position in the investigator office [28,29,45] or during 24h-ambulatory monitoring [44][45][46][47] (Table 2). It has been suggested that circadian BP rhythm may represent a possible key target of SGLT2 inhibitors used for the treatment of Type 2 diabetes [48].…”

Reappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics

“…On average, a mild diuretic effect was observed with ertugliflozin 1 mg and 25 mg (24-h urinary volume increase: 126.5 mL and 236.2 mL, respectively), but not with HCTZ (−1.73 mL/day). No significant changes in 24-h mean plasma renin activity or urinary aldosterone were seen with either ertugliflozin or HCTZ [29].…”

“…A 4-week study compared the BP-lowering effects of ertugliflozin (1 mg, 5 mg, 25 mg), HCTZ (12.5 mg) and a placebo in 194 patients with T2D and hypertension [29]. Reductions in SBP were closely similar with ertugliflozin and HCTZ ( Table 2).…”

“…Probably in reaction to extracellular volume contraction and reduced arterial pressure, SGLT2 inhibition activates systemic and local renin-angiotensin-aldosterone system (RAAS) activity in diabetic patients similar to what is observed with HCTZ treatment [28], despite reports of controversial results [29]. It has been speculated that RAAS activation during ACE inhibition or angiotensin II receptor blockade might favour cardioprotective pathways of the RAAS cascade, including angiotensin-(1-7) production, macrophage activation syndrome (MAS) and angiotensin II receptor type 2 (AT2 receptors) [59].…”