Cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs according to baseline blood pressure in type 2 diabetes: a systematic meta-analysis of cardiovascular outcome trials

Abstract

Objectives: Using a systematic meta-analysis, we investigated if patients with type 2 diabetes (T2D) and with varying baseline blood pressure (BP) differ in the cardiorenal benefits received from sodium–glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs). Design: Randomized, placebo-controlled, cardiovascular outcome trials (CVOTs) of SGLT-2is and GLP-1RAs were identified from MEDLINE, Embase, and the Cochrane Library up to April 2024. Hazard ratios (HRs) with 95% CIs were pooled. The differential treatment effect by baseline BP category within each trial was estimated as the ratio of the HR (RHR) and pooled. Results: Seventeen publications based on 9 unique CVOTs (4 SGLT-2is and 5 GLP-1RAs) were eligible. In participants with normal baseline BP, comparing SGLT-2is with placebo, the HRs (95% CIs) were 0.88 (0.79-0.97) for major adverse cardiovascular events (MACE), 0.73 (0.59-0.91) for heart failure (HF) hospitalization, 0.78 (0.65-0.94) for composite CVD death/HF hospitalization, and 0.55 (0.41-0.73) for composite renal outcome. The corresponding estimates for participants with higher baseline BP were 0.88 (0.81-0.96), 0.67 (0.57-0.79), 0.73 (0.65-0.82), and 0.61 (0.48-0.77), respectively. In participants with normal baseline BP, GLP-RAs had no strong effect on MACE, stroke and nephropathy, but reduced stroke and nephropathy risk in those with higher baseline BP. Estimated RHRs showed no statistical evidence that baseline BP modified the cardiorenal benefits of SGLT-2is and GLP-1RAs. Conclusions: In patients with T2D, the cardiorenal benefits of treatment with SGLT2-Is and GLP1-RAs were similar in patients with normal baseline BP compared to those with a higher baseline BP.