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; <0.001 for both) and diastolic BP (weighted mean difference, -0.898 and -2.279 mm Hg, respectively; <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; <0.001 for both). In SGLT2i treatment, weight loss was significantly associated with systolic BP reduction (β=0.820; =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.