CoChat
Sign Up
Cited by 255Blood Pressure and Hypertension StudiesDiabetes Treatment and ManagementHeart Failure Treatment and Management

Twenty-Four-Hour Blood Pressure–Lowering Effect of a Sodium-Glucose Cotransporter 2 Inhibitor in Patients With Diabetes and Uncontrolled Nocturnal Hypertension: Results From the Randomized, Placebo-Controlled SACRA Study

Open access
Kario, Kazuomi, Okada, Kenta, Kato, Mitsutoshi, Nishizawa, Masafumi, Yoshida, Tetsuro, Asano, Tsuguyoshi, Uchiyama, Kazuaki, Niijima, Yawara +17 more·2019·Circulation
DOI 10.1161/circulationaha.118.037076PMC PMC6493695
Open this paper in CoChat — free account

Abstract

Background: The risk of cardiovascular disease and mortality in salt-sensitive patients with diabetes mellitus and uncontrolled nocturnal hypertension is high. The SACRA (Sodium-Glucose Cotransporter 2 [SGLT2] Inhibitor and Angiotensin Receptor Blocker [ARB] Combination Therapy in Patients With Diabetes and Uncontrolled Nocturnal Hypertension) study investigated changes in blood pressure (BP) with empagliflozin plus existing antihypertensive therapy. Methods: This multicenter, double-blind, parallel study was conducted in Japan. Adult patients with type 2 diabetes mellitus and uncontrolled nocturnal hypertension receiving stable antihypertensive therapy including angiotensin receptor blockers were randomized to 12 weeks’ treatment with empagliflozin 10 mg once daily or placebo. Clinic BP was measured at baseline and weeks 4, 8, and 12; 24-hour ambulatory BP monitoring was performed at baseline and week 12; and morning home BP was determined for 5 days before each visit. The primary efficacy end point was change from baseline in nighttime BP (ambulatory BP monitoring). Results: One hundred thirty-two nonobese, older patients with well-controlled blood glucose were randomized (mean age 70 years, mean body mass index 26 kg/m 2 ). Empagliflozin, but not placebo, significantly reduced nighttime systolic BP versus baseline (–6.3 mm Hg; P =0.004); between-group difference in change from baseline was –4.3 mm Hg ( P =0.159). Reductions in daytime, 24-hour, morning home, and clinic systolic BP at 12 weeks with empagliflozin were significantly greater than with placebo (–9.5, –7.7, –7.5, and –8.6 mm Hg, respectively; all P ≤0.002). Between-group differences in body weight and glycosylated hemoglobin reductions were significant, but small (–1.3 kg and –0.33%; both P <0.001). At 4 weeks, N-terminal pro-B-type natriuretic peptide levels were reduced to a greater extent in the empagliflozin versus placebo group (–12.1%; P =0.013); atrial natriuretic peptide levels decreased with empagliflozin versus placebo at weeks 4 and 12 (–8.2% [ P =0.008] and –9.7% [ P =0.019]). Changes in antihypertensive medication during the study did not differ significantly between groups. Conclusions: Nonseverely obese older diabetes patients with uncontrolled nocturnal hypertension showed significant BP reductions without marked reductions in glucose with the addition of empagliflozin to existing antihypertensive and antidiabetic therapy. Use of sodium-glucose cotransporter 2 inhibitors in specific groups (eg, those with nocturnal hypertension, diabetes, and high salt sensitivity) could help reduce the risk of heart failure and cardiovascular mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03050229.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/circulationaha.118.037076

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 [225]

  • SGLT2 inhibitors induced a larger blood-pressure decrease than did GLP-1 receptor agonists without changing heart rate.

    “SGLT2 inhibitors induced a larger BP decrease than did GLP-1 RAs without changing heart rate.”

    From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [225]

  • Favorable effects on arterial stiffness, vascular resistance, and blood pressure variability have been observed in human clinical trials of SGLT2 inhibitors.

    “This is further supported by favorable effects on arterial stiffness, vascular resistance, and BP variability in human clinical trials.[32][33][34]”

    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 [34]

  • Human trials show SGLT2 inhibitors improve arterial stiffness, vascular resistance, endothelial function, and blood pressure variability.

    “Human clinical trials have shown that SGLT2 inhibitors exert favorable effects on arterial stiffness, vascular resistance, and endothelial and blood pressure variability (Kario et al., 2018; Chilton et al., 2015; Cherney et al., 2014a; Cooper et al., 2019).”

    From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Kario et al., 2018

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kario, K., Okada, K., Kato, M., Nishizawa, M., Yoshida, T., Asano, T., Uchiyama, K., Niijima, Y., Katsuya, T., Urata, H., Osuga, J.-I., Fujiwara, T., Yamazaki, S., Tomitani, N., Kanegae, H., Hoshide, S., Yamamoto, M., Eguchi, K., Mizuno, A., Nakano, S., Kemi, Y., Iwashita, C., Wada, K., Kaneko, A., & Ryan, N.
Affiliations
  • Jichi Medical University (JP)
  • Kato Clinic of Internal Medicine, Tokyo, Japan (M.K.).
  • Asano Kanamachi Clinic, Tokyo, Japan (T.A.).
  • Uchiyama Clinic, Niigata, Japan (K.U.).
  • Kan-etsu Chuoh Hospital, Gunma, Japan (Y.N.).
  • The University of Osaka (JP)
  • Fukuoka University (JP)
  • Utsunomiya Higashi Hospital, Tochigi, Japan (J.O.).
Corresponding author
Kario, Kazuomi
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-04-30
Volume
139
Issue
18
Pages
2089-2097
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.118.037076
PMC
PMC6493695
OpenAlex
W2903192033
Cited by
251
References
37
Citations by year
2026: 15 · 2025: 28 · 2024: 23 · 2023: 40 · 2022: 45 · 2021: 42 · 2020: 37 · 2019: 20 · 2017: 1
FWCI
26.03
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Circulation (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (16K09514)
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
empagliflozin, SGLT2 inhibitors, nocturnal hypertension, type 2 diabetes, blood pressure reduction, ambulatory blood pressure monitoring, angiotensin receptor blockers, N-terminal pro-brain natriuretic peptide, atrial natriuretic peptide, body weight, HbA1c, cardiovascular risk, salt-sensitive hypertension, older adults

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review