Blood pressure-lowering effects of SGLT2 inhibitors and GLP-1 receptor agonists for preventing of cardiovascular events and death in type 2 diabetes: a systematic review and meta-analysis

Aims To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of major cardiovascular event stratified by glucose-lowering drugs, baseline BP, glycated hemoglobin (HbA 1c ), and history of cardiovascular disease in patients with type 2 diabetes. Methods We performed a systematic review of the MEDLINE and EMBASE databases search up to December 31, 2022, (PROSPERO, CRD42023400899) to identify all large-scale cardiovascular outcomes (CVO) trials of SGLT2i and GLP-1 RAs in which more than 1,000 patient-years of follow-up in each randomized group. Outcomes included all-cause mortality, major adverse cardiovascular event (MACE) and its component (cardiovascular death, myocardial infarction [MI], and stroke), heart failure, and renal failure. A random-effects meta-analyses were used to pool the estimates. Results Eighteen CVOTs (ten for SGLT2i and eight for GLP-1 RAs) with 127,606 patients with type 2 diabetes were included. Over 2.5 years median follow-up, the average reduction of systolic BP was 2.2 mmHg (mean difference [MD] − 2.2; 95% CI − 2.7 to − 1.7) with more important reduction ( P interaction = 0.001) with SGLT2 inhibitors (− 2.9; − 3.4 to − 2.5) than with GLP-1 RAs (− 1.4; − 1.8 to − 1). With SGLT2i, every 5-mmHg reduction in systolic BP was associated with a significantly lower risk of mortality (hazard ratio[HR], 0.77; 95% CI 0.65–0.90), MACE (HR 0.81 [0.74–0.89]), cardiovascular death (HR 0.72 [0.59–0.88]), MI (HR 0.82 [0.71–0.95]), heart failure (HR 0.49 [0.42–0.57]), and renal failure (HR 0.46 [0.38–0.55]), while the association was not significant for stroke (HR 0.91 [0.69–1.19]). The corresponding effects for every 5-mmHg reduction in SBP with GLP-1 RAs were 0.65 (0.51–0.84) for all-cause mortality, 0.65 (0.56–0.76) for MACE, 0.62 (0.45–0.85) for CV death, 0.71 (0.52–0.76) for MI, 0.49 (0.35–0.69) for stroke, and 0.49 (0.35–0.66) for renal failure, while the association was not significant for heart failure (HR 0.82 [0.63–1.08]). Conclusion In patients with type 2 diabetes, the hypotensive effects of SGLT2i and GLP-1 RAs were significantly associated with a reduction in mortality and cardiorenal events. These findings suggest that the lowering BP effect could be seen as an additive indicator of cardiovascular protection by SGLT2i and GLP-1 RAs drugs.