Ambulatory blood pressure reduction with SGLT-2 inhibitors: dose-response meta-analysis and comparative evaluation with low-dose hydrochlorothiazide
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OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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A recent meta-analysis including seven randomized controlled trials demonstrated that SGLT2 inhibitors were associated with an average reduction of 3.6/1.7 mmHg systolic/diastolic in 24-hour ambulatory blood pressure, comparable with efficacy of low-dose hydrochlorothiazide.
“A recent meta-analysis including seven RCTs demonstrated that SGLT2 inhibitors were associated with an average reduction of 3.6/1.7 mmHg (systolic/diastolic) in 24 h ambulatory BP, which is comparable with efficacy of low-dose hydrochlorothiazide.”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [226]
Similar findings have been reported in short-term trials of other SGLT2 inhibitors, and longer-term blood pressure-lowering effects in type 2 diabetes with relatively preserved kidney function have been demonstrated in large cardiovascular outcome trials.
“Similar findings have been reported in short-term trials of other SGLT2 inhibitors, 6,18,19 and the longer-term BP lowering effects of SGLT2 inhibitors in individuals with T2DM and relatively preserved kidney function have been demonstrated in large cardiovascular outcome trials.5,20,21”
From Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial (2021) · cites this paper as [18]
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Self-citation
- Authors
- Georgianos, P. I., & Agarwal, R.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Richard L. Roudebush VA Medical Center (US)
- Corresponding author
- Agarwal, Rajiv
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2019-03-11
- Volume
- 42
- Issue
- 4
- Pages
- 693-700
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC6429633
- OpenAlex
- W2923754537
- Cited by
- 130
- References
- 26
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 25 · 2023: 16 · 2022: 23 · 2021: 16 · 2020: 14 · 2019: 4
- FWCI
- 10.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- PMC
- Funders
- National Heart, Lung, and Blood Institute
- VA (5I01CX000829-04)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- SGLT2 inhibitors, ambulatory blood pressure, blood pressure reduction, dose-response relationship, sodium excretion, diurnal blood pressure variation, antihypertensive drugs, systolic and diastolic blood pressure
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Blood Pressure, Humans, Hydrochlorothiazide, Hypertension, Randomized Controlled Trials as Topic, Blood Pressure Monitoring, Ambulatory
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