Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta-Analysis

J Am Heart Assoc. 2020 Apr 7;9(7):e015323. doi: 10.1161/JAHA.119.015323. Epub 2020 Mar 30.

Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (BP)-lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with GLP-1RA treatment and SGLT2i treatment on BP changes in patients with type 2 diabetes mellitus. Methods and Results Studies were identified by a search of MEDLINE, EMBASE, and the Cochrane Central Register until June 2019. Meta-regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of BP. A total of 184 trials were included. Both GLP-1RA and SGLT2i led to significant reductions in systolic BP (weighted mean difference, -2.856 and -4.331 mm Hg, respectively; P<0.001 for both) and diastolic BP (weighted mean difference, -0.898 and -2.279 mm Hg, respectively; P<0.001 for both). For both drug classes, hemoglobin A1c reduction was not independently associated with systolic BP reduction or diastolic BP reduction. In GLP-1RA treatment, weight reduction was positively associated with systolic BP reduction and diastolic BP reduction (β=0.821 and β=0.287, respectively; P<0.001 for both). In SGLT2i treatment, weight loss was significantly associated with systolic BP reduction (β=0.820; P=0.001) but was not associated with diastolic BP reduction. Conclusions Treatment with GLP-1RA and SGLT2i led to significant reductions in BP in patients with type 2 diabetes mellitus. Weight reduction was significantly and independently associated with BP reductions in GLP-1RA treatment and SGLT2i treatment.

Keywords: blood pressure; glucagon‐like peptide‐1 receptor agonists; meta‐analysis; sodium‐glucose cotransporter‐2 inhibitors; type 2 diabetes mellitus.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Biomarkers
  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Incretins
  • Sodium-Glucose Transporter 2 Inhibitors
  • hemoglobin A1c protein, human