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

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.