Influence of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on the management of blood pressure in Japanese patients with diabetes.
This post hoc analysis of the RECAP study examined how combination therapy with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and a glucagon-like peptide-1 receptor agonist (GLP-1RA) affected blood pressure (BP) control in Japanese patients with type 2 diabetes (T2D) and hypertension. Of 643 T2D patients in the original study, 431 with baseline hypertension were analyzed. Patients were grouped by which drug class was initiated first (GLP-1RA-preceding, n=207; SGLT2i-preceding, n=224). The study found that the rate of achieving the target office BP of less than 130/80 mmHg increased significantly from 25.4% after single-agent therapy to 33.3% after combination therapy was established. Office BP declined from 141.8/82.4 mmHg at baseline to 131.7/79.4 mmHg following combination therapy, and home systolic BP also decreased significantly. Propensity score-based inverse probability weighting analysis revealed no significant difference in BP outcomes based on which drug class was initiated first. Key limitations include the post hoc, non-randomized design, the single-ethnicity Japanese population, and potential residual confounding despite statistical adjustment.
Why this grade: Although conducted in humans with a reasonably sized cohort, this is a post hoc, non-randomized observational analysis with no control arm, limiting causal inference about the combination therapy's effect on blood pressure.
Combination therapy with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) is increasingly used to prevent cardiovascular events. Our previous study demonstrated the renal benefits of this combination therapy. Both drug classes exert pleiotropic effects on metabolic factors, such as obesity and hypertension; however, the impact of this combination therapy on blood pressure (BP) has not been fully evaluated. This post hoc analysis aimed to assess the effects of SGLT2i-GLP-1RA combination therapy on BP control in patients with type 2 diabetes (T2D). Among the 643 T2D patients enrolled in the RECAP study, 431 with baseline hypertension were analyzed (GLP-1RA-preceding group, n = 207; SGLT2i-preceding group, n = 224). The achievement rate of the target office BP ( < 130/80 mmHg) after the initiation of combination therapy was evaluated using multiple imputations. Changes in office and home BP were analyzed using generalized linear mixed models. The influence of preceding treatment was assessed using propensity score-based inverse probability weighting (PS-IPW). The achievement rate of the target BP increased from 25.4% after treatment to 33.3% after combination therapy (p = 0.003). Office BP decreased from 141.8/82.4 mmHg at baseline to 135.2/78.5 mmHg after treatment addition and 131.7/79.4 mmHg after combination therapy (all p < 0.001). The home systolic BP also significantly decreased (p = 0.03). PS-IPW analysis showed no significant differences in BP outcomes or target achievement rates according to the preceding treatment. Collectively, SGLT2i-GLP-1RA combination therapy significantly improved BP control, independent of the order in which the agents were initiated.
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