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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 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
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Fig1: 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

Mentions: The SGLT2 inhibitors in the present study were ipragliflozin in seven patients, dapagliflozin in six patients, tofogliflozin in four patients, and luseogliflozin in three patients. Figure 1 shows the changes in HbA1c level, body weight, and BP up to 6 months after administration of SGLT2 inhibitors. The HbA1c level began to decrease significantly at 1 month (8.5 ± 1.2%, P = 0.0014) and was still significantly decreased at 3 months (8.3 ± 1.2%, P < 0.0001). Although the HbA1c level at 6 months (8.5 ± 1.1%) was slightly increased compared with that at 3 months, it remained significantly decreased compared with the pre-administration level (P < 0.0001). Body weight was significantly decreased at 1 month (89.5 ± 22.1 kg, P < 0.0001), 3 months (88.4 ± 22.3 kg, P < 0.0001), and 6 months (87.6 ± 21.4 kg, P < 0.0001) compared with baseline. SBP decreased significantly at 1 month (123.2 ± 9.8 mmHg, P = 0.0314), 3 months (123.2 ± 11.7 mmHg, P = 0.0311), and 6 months (118.6 ± 11.0 mmHg, P = 0.0041) compared with pre-administration BP. DBP at 6 months (68.4 ± 9.3 mmHg) was significantly decreased compared with that at baseline (74.4 ± 10.4 mmHg, P = 0.0363), 1 month (73.4 ± 8.5 mmHg, P = 0.0456), and 3 months (73.4 ± 8.6 mmHg, P = 0.0101).Fig. 1


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

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5385592&req=5

Fig1: 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
Mentions: The SGLT2 inhibitors in the present study were ipragliflozin in seven patients, dapagliflozin in six patients, tofogliflozin in four patients, and luseogliflozin in three patients. Figure 1 shows the changes in HbA1c level, body weight, and BP up to 6 months after administration of SGLT2 inhibitors. The HbA1c level began to decrease significantly at 1 month (8.5 ± 1.2%, P = 0.0014) and was still significantly decreased at 3 months (8.3 ± 1.2%, P < 0.0001). Although the HbA1c level at 6 months (8.5 ± 1.1%) was slightly increased compared with that at 3 months, it remained significantly decreased compared with the pre-administration level (P < 0.0001). Body weight was significantly decreased at 1 month (89.5 ± 22.1 kg, P < 0.0001), 3 months (88.4 ± 22.3 kg, P < 0.0001), and 6 months (87.6 ± 21.4 kg, P < 0.0001) compared with baseline. SBP decreased significantly at 1 month (123.2 ± 9.8 mmHg, P = 0.0314), 3 months (123.2 ± 11.7 mmHg, P = 0.0311), and 6 months (118.6 ± 11.0 mmHg, P = 0.0041) compared with pre-administration BP. DBP at 6 months (68.4 ± 9.3 mmHg) was significantly decreased compared with that at baseline (74.4 ± 10.4 mmHg, P = 0.0363), 1 month (73.4 ± 8.5 mmHg, P = 0.0456), and 3 months (73.4 ± 8.6 mmHg, P = 0.0101).Fig. 1

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.