Effects of Sodium-Glucose Cotransporter 2 Inhibitors on 24-Hour Ambulatory Blood Pressure: A Systematic Review and Meta-Analysis

J Am Heart Assoc. 2017 May 18;6(5):e005686. doi: 10.1161/JAHA.117.005686.

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP.

Methods and results: We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP. We searched all studies published before August 17, 2016, which reported 24-hour ambulatory BP data. Mean differences in 24-hour BP, daytime BP, and nighttime BP were calculated by a random-effects model. SGLT2 inhibitors significantly reduce 24-hour ambulatory systolic and diastolic BP by -3.76 mm Hg (95% CI, -4.23 to -2.34; I2=0.99) and -1.83 mm Hg (95% CI, -2.35 to -1.31; I2=0.76), respectively. Significant reductions in daytime and nighttime systolic and diastolic BP were also found. No association between baseline BP or change in body weight were observed.

Conclusions: This meta-analysis shows that the reduction in 24-hour ambulatory BP observed with SGLT2 inhibitors is a class effect. The diurnal effect of SGLT2 inhibitors on 24-hour ambulatory BP may contribute to their favorable effects on cardiovascular outcomes.

Keywords: ambulatory blood pressure monitoring; diabetes mellitus; diabetic therapy/glitazones; high blood pressure; hypertension; metformin; sodium‐glucose cotransporter 2 inhibitors.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / therapeutic use
  • Blood Pressure / drug effects*
  • Blood Pressure Monitoring, Ambulatory
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Canagliflozin / therapeutic use
  • Circadian Rhythm*
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / physiopathology
  • Female
  • Glucosides / therapeutic use
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / physiopathology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Glucosides
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin
  • dapagliflozin
  • ertugliflozin
  • empagliflozin