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

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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.

No MeSH data available.


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
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Fig2: 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

Mentions: Figure 2 shows the changes in urinary data up to 6 months after administration of SGLT2 inhibitors. The urine volume was significantly increased at 2 weeks (3752 ± 1815 mL/day, P < 0.0001) and 6 months (4294 ± 2151 mL/day, P < 0.0001) after administration of SGLT2 inhibitors compared with baseline (2309 ± 1186 mL/day). The urinary excretion of glucose at 2 weeks (172.5 ± 107.7 g/day, P < 0.0001) and 6 months (182.2 ± 150.3 g/day, P < 0.0001) was significantly increased compared with baseline (46.2 ± 60.9 g/day). Furthermore, the urinary excretion of sodium at 2 weeks (15.9 ± 8.9 g/day, P = 0.0266) and 6 months (16.1 g/day, P = 0.0206) was also significantly increased compared with baseline (11.5 ± 6.1 g/day).Fig. 2


Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes
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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5385592&req=5

Fig2: 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
Mentions: Figure 2 shows the changes in urinary data up to 6 months after administration of SGLT2 inhibitors. The urine volume was significantly increased at 2 weeks (3752 ± 1815 mL/day, P < 0.0001) and 6 months (4294 ± 2151 mL/day, P < 0.0001) after administration of SGLT2 inhibitors compared with baseline (2309 ± 1186 mL/day). The urinary excretion of glucose at 2 weeks (172.5 ± 107.7 g/day, P < 0.0001) and 6 months (182.2 ± 150.3 g/day, P < 0.0001) was significantly increased compared with baseline (46.2 ± 60.9 g/day). Furthermore, the urinary excretion of sodium at 2 weeks (15.9 ± 8.9 g/day, P = 0.0266) and 6 months (16.1 g/day, P = 0.0206) was also significantly increased compared with baseline (11.5 ± 6.1 g/day).Fig. 2

View Article: PubMed Central - PubMed

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&thinsp;&plusmn;&thinsp;10.7&nbsp;years, BMI 33.0&thinsp;&plusmn;&thinsp;4.9&nbsp;kg/m2) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2&nbsp;weeks and 6&nbsp;months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6&nbsp;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&nbsp;weeks and 6&nbsp;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&thinsp;&plusmn;&thinsp;11.0 to 123.2&thinsp;&plusmn;&thinsp;9.8&nbsp;mmHg, P&thinsp;=&thinsp;0.0314), but diastolic BP (DBP) did not (74.4&thinsp;&plusmn;&thinsp;10.4 to 73.4&thinsp;&plusmn;&thinsp;8.5&nbsp;mmHg, P&thinsp;=&thinsp;0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R&thinsp;=&thinsp;&minus;0.62, P&thinsp;=&thinsp;0.0073), but not increased urinary sodium excretion. At 6&nbsp;months, SBP (118.6&thinsp;&plusmn;&thinsp;11.0&nbsp;mmHg, P&thinsp;=&thinsp;0.0041) and DBP (68.4&nbsp;mmHg, P&thinsp;=&thinsp;0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R&thinsp;=&thinsp;&minus;0.60, P&thinsp;=&thinsp;0.0014), but not increased urinary glucose excretion.

Conclusions: SGLT2 inhibitors significantly decreased SBP after 1&nbsp;month and DBP after 6&nbsp;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&nbsp;weeks and by natriuresis at 6&nbsp;months after SGLT2 inhibitor administration.

No MeSH data available.