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. 2017 Apr 10;18(1):23.
doi: 10.1186/s40360-017-0125-x.

Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes

Shin Kawasoe  1 , Yukiko Maruguchi  2 , Shoko Kajiya  2 , Hitoshi Uenomachi  2 , Masaaki Miyata  3 , Mariko Kawasoe  1 , Takuro Kubozono  1 , Mitsuru Ohishi  1
Affiliations

Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes

Shin Kawasoe et al. BMC Pharmacol Toxicol. .

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients.

Methods: Twenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m2) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2 weeks and 6 months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6 months after SGLT2 inhibitor administration. We evaluated the changes in urine volume and urinary excretion of glucose and sodium as well as correlations among urine volume and urinary sodium glucose excretion at 2 weeks and 6 months after administration of the SGLT2 inhibitors. Furthermore, we investigated the correlations between changes in BP and urinary excretion of sodium and glucose at the same time.

Results: Two weeks after administration, systolic BP (SBP) significantly decreased (128.5 ± 11.0 to 123.2 ± 9.8 mmHg, P = 0.0314), but diastolic BP (DBP) did not (74.4 ± 10.4 to 73.4 ± 8.5 mmHg, P = 0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R = -0.62, P = 0.0073), but not increased urinary sodium excretion. At 6 months, SBP (118.6 ± 11.0 mmHg, P = 0.0041) and DBP (68.4 mmHg, P = 0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R = -0.60, P = 0.0014), but not increased urinary glucose excretion.

Conclusions: SGLT2 inhibitors significantly decreased SBP after 1 month and DBP after 6 months in obese patients with type 2 diabetes. The main mechanism of the BP-lowering effect may be plasma volume reduction by osmotic diuresis at 2 weeks and by natriuresis at 6 months after SGLT2 inhibitor administration.

Keywords: Blood pressure; Natriuresis; Osmotic diuresis; SGLT2 inhibitor; Type 2 diabetes.

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Figures

Fig. 1
Fig. 1
Changes in glycosylated hemoglobin, body weight, and BP up to 6 months after administration of sodium-glucose cotransporter 2 inhibitors (n = 20). HbA1c, glycosylated hemoglobin; BP, blood pressure; M, months. *, P < 0.05; **, P < 0.01
Fig. 2
Fig. 2
Changes in 24-h urinary collection data up to 6 months after administration of sodium-glucose cotransporter 2 inhibitors (n = 20). W, weeks; M, months; *, P < 0.05; **, P < 0.01
Fig. 3
Fig. 3
Relationship between changes in urine volume and urinary excretion of sodium and glucose 2 weeks (a) and 6 months (b) after administration of sodium-glucose cotransporter 2 inhibitors (n = 20)
Fig. 4
Fig. 4
Relationship between changes in BP and urinary excretion of sodium and glucose 2 weeks (a) and 6 months (b) after administration of sodium-glucose cotransporter 2 inhibitors (n = 18). BP, blood pressure
Fig. 5
Fig. 5
Changes of blood pressure with or without antihypertensive drugs 6 months after administration of sodium-glucose cotransporter 2 inhibitors (N = 20). BP, blood pressure; M, months; *, P < 0.05
Fig. 6
Fig. 6
The clinical courses of four patients who could stop (A, B) or reduce (C, D) the amount of anti-hypertensive drugs. SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1C, glucosylated hemoglobin
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