Abstract
Objective: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). We aimed at providing precise effect estimates regarding the effect of their combination on office blood pressure levels. Design and method: PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration equal to or greater than 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. Results: We identified three eligible RCTs (namely, AWARD-10, DURATION-8 and SUSTAIN 9 trials), pooling data retrieved from 1,042 patients with T2DM in total. All studies were rated as low risk of bias. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in a significant decrease in systolic blood pressure levels by 3.64 mmHg (95% CI: -6.24 to -1.03, I^2 = 68%), although it did not have a significant impact on diastolic blood pressure levels (mean difference= -0.51, 95% CI: -1.51 to 0.49, I^2 = 0%). Conclusions: Both SGLT-2i and GLP-1Ras have provided remarkable results regarding their cardiovascular efficacy in hallmark cardiovascular outcome trials recently. However, there are no data regarding the cardiovascular efficacy of their combination, questioning whether those two drug classes exhibit additive cardioprotective effects. The present meta-analysis suggests a significant, additive effect on systolic blood pressure levels. Further RCTs are required in order to shed light on this hypothesis.
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