Efficacy and safety evaluation of SGLT2i on blood pressure control in patients with type 2 diabetes and hypertension: a new meta-analysis

Abstract

Background The clinical efficacy and safety of SGLT2i in treating patients with type 2 diabetes mellitus and hypertension lack immense data support. Objective To systematically evaluate the clinical efficacy and safety of SGLT2i in patients with type 2 diabetes mellitus and hypertension by collecting the previously published randomized controlled trials on SGLT2i to provide data support for SGLT2i as an adjuvant in the first-line antihypertensive regimen in patients with type 2 diabetes mellitus and hypertension. Methods Randomized controlled trials comparing SGLT2i with a placebo in treating type 2 diabetes with hypertension were screened strictly according to inclusion and exclusion criteria. The primary efficacy endpoints included 24H systolic blood pressure, 24H diastolic blood pressure, office systolic blood pressure, and office diastolic blood pressure. The secondary efficacy endpoints included HbA1c. The safety indicators were hypoglycemia, urinary tract infection, genital infection, and renal impairment.MD was the combined effect size for continuous variables, and RR was the combined effect size for dichotomous variables. Results 10 RCTs with 9913 participants (6293 in the SGLT2i group and 3620 in the control group) were included for analysis.SGLT2i is effective in reducing blood pressure compared with placebo in patients with type 2 diabetes and hypertension, 24HSBP (− 5.06 mmHg, 95% CI [− 7.10, − 3.01], t = − 6.19, P < 0.05), 24HDBP (− 2.39 mmHg, 95% CI [− 4.11, − 0.67], t = − 4.15, P = 0.004), Office SBP (− 4.53 mmHg, 95% CI [− 5.66, − 3.40], t = − 9.50, P < 0.05), Office DBP (− 2.12 mmHg, 95% CI [− 3.42, − 0.82], t = − 4.88, P = 0.001). HbA1c decreased significantly (− 0.57%, 95% CI [− 0.60, − 0.54], z = 37.02, p < 0.01). SGLT2i did not increase hypoglycemia compared to placebo (RR = 1.22, 95% CI [0.916, 1.621], z = 1.36 p = 0.174), urinary tract infection (RR = 1.56, 95% CI [0.96, 2.52], z = 1.79 p = 0.073), risk of renal injury (RR = 0.78, 95% CI [0.54, 1.13], Z = 1.31, P = 0.19), but the risk of genital tract infection increased by 2.32 times (RR = 2.32, 95% CI [1.57, 3.42], Z = 4.23, P = 0.00). Conclusion SGLT2i can effectively control blood pressure and blood glucose and generally has high safety. For patients with type 2 diabetes mellitus and hypertension with a low risk of genital infection, SGLT2i should be considered as an adjuvant drug for a first-line antihypertensive regimen.

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“…SGLT2 inhibitors have shown blood pressure-lowering effects [19]. We did not find significant changes of blood pressure, which was measured as office blood pressure and not the primary focus of the study.…”

Sodium-Glucose Cotransporter 2 Inhibitors' Mechanism of Action and Use in Kidney Transplantation Recipients: Extended Review and Update

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The relationship between SGLT2 and systemic blood pressure regulation

“…Instead, it travels through the nephron, is excreted through the urine, and subsequently decreases blood sugar. Recent research revealed that in addition to reducing blood sugar, SGLT2i also decreases blood pressure in diabetic hypertensive individuals [31]. The mechanism by which blood pressure is decreased is not entirely understood, but it is possible that osmotic and natriuretic diuresis decreases circulating plasma volume eventually leading to decreased blood pressure [32,33].…”