SGLT2 Inhibitor and ARB Combination Therapy in Patients With Diabetes and Uncontrolled Nocturnal Hypertension - SACRA

Jan 16, 2019
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
Date Published:
11/28/2018
Date Updated:
01/16/2019
Original Posted Date:
01/16/2019
References

Contribution To Literature:

The SACRA trial showed that empagliflozin resulted in significant reduction in nighttime SBP and DBP compared with baseline among patients with DM2 and uncontrolled nighttime BP, but the difference compared with placebo was not statistically significant.

Description:

The goal of the trial was to assess the efficacy of empagliflozin in reducing hypertension in patients with type 2 diabetes mellitus (DM2) and uncontrolled nocturnal hypertension.

Study Design

Patients were randomized in a 1:1 fashion to either empagliflozin 10 mg daily (n = 68) or matching placebo (n = 63).

  • Total number screened: 174
  • Total number of enrollees: 131
  • Duration of follow-up: 12 weeks
  • Mean patient age: 70 years
  • Percentage female: 48%

Inclusion criteria:

  • Age ≥20 years
  • DM2
  • Glycosylated hemoglobin (HbA1c) ≥6 and <10%
  • Seated blood pressure (BP) 130-159/80-99 mm Hg
  • Nocturnal hypertension (systolic BP [SBP] >115 mm Hg at 2:00, 3:00, and 4:00 am during sleep 5 days prior to randomization measured using home BP monitor)
  • Stable antidiabetic measurement
  • Stable antihypertensive treatment that included an angiotensin-receptor blocker (ARB) for ≥8 weeks prior to baseline

Exclusion criteria:

  • History of diabetic ketoacidosis or diabetic coma
  • Renal and liver damage
  • Cardiovascular disease event within 3 months

Other salient features/characteristics:

  • Median duration of diabetes: 10 years
  • HbA1c: 6.6%
  • Known cardiac disease: 16%
  • Diabetes medications: DPP-4: 54%, metformin: 28%
  • Hypertension medications:  calcium channel blocker: 68%

Principal Findings:

The primary outcome, change from baseline to week 12 in nighttime SBP for empagliflozin vs. placebo, -6.3 vs. -2.0 mm Hg, between group difference: -4.3 mm Hg, p = 0.16

Secondary outcomes for empagliflozin vs. placebo:

  • HbA1c: 6.39% vs. 6.7%, p < 0.001
  • Change in daytime SBP at week 12 from baseline: -11.7 vs. -2.1, p < 0.001
  • Change in nighttime diastolic BP [DBP] at week 12 from baseline: -2.5 vs. -0.9, p = 0.28

Interpretation:

The results of this trial indicate that empagliflozin resulted in significant reduction in nighttime SBP and DBP compared with baseline among patients with DM2 and uncontrolled nighttime BP, but the difference compared with placebo was not statistically significant. These data add to the growing literature on the cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT-2) inhibitors among high-risk patients with DM2; in this case, the additional risk was hypertension.

References:

Kario K, Okada K, Kato M, et al. 24-Hour Blood Pressure-Lowering Effect of an SGLT-2 Inhibitor in Patients with Diabetes and Uncontrolled Nocturnal Hypertension: Results from the Randomized, Placebo-Controlled SACRA Study. Circulation 2018;Nov 28:[Epub ahead of print].

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Hypertension

Keywords: Angiotensin II Type 1 Receptor Blockers, Antihypertensive Agents, Benzhydryl Compounds, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Diabetes Mellitus, Type 2, Hemoglobin A, Hypertension, Hypoglycemic Agents, Metabolic Syndrome, Primary Prevention


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