Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide

• Published in: Diabetes care Vol. 42; no. 4; pp. 693 - 700
• Main Authors: Georgianos, Panagiotis I, Agarwal, Rajiv
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-04-2019
• Subjects: Blood pressure; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Cardiovascular diseases; Clinical trials; Evaluation; Humans; Hydrochlorothiazide; Hydrochlorothiazide - therapeutic use; Hypertension - drug therapy; Inhibition; Inhibitors; Medical research; Meta-Analysis; Na+/glucose cotransporter; Pressure reduction; Randomized Controlled Trials as Topic; Research design; Sodium; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Subgroups
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc18-2207

Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide.
PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP.
We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality.
This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide.