Key result
GLP-1 RAs cut MACE ~22% vs. placebo, with consistent benefit regardless of SGLT2i use.
Why the study?
Do GLP-1 receptor agonists reduce cardiovascular events in patients with type 2 diabetes independently of background SGLT2 inhibitor use?
Meta-Analysis (n=13,538)
Do GLP-1 receptor agonists reduce cardiovascular events in patients with type 2 diabetes independently of background SGLT2 inhibitor use?
Hazard Ratio: 0.78 (95% CI 0.49–1.24)
p-value: p=0.95 for interaction
GLP-1 receptor agonists reduce major adverse cardiovascular events in patients with type 2 diabetes independently of background SGLT2 inhibitor use.
BACKGROUND Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear. OBJECTIVES The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors. METHODS Post hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use. RESULTS Of the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18). CONCLUSIONS In patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed.
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Neves et al. (2023) conducted a meta-analysis in Type 2 diabetes and cardiovascular or renal disease (n=13,538). GLP-1 receptor agonists vs. Placebo was evaluated on Major adverse cardiovascular events (composite of cardiovascular death, myocardial infarction, or stroke) (HR 0.78, 95% CI 0.49-1.24, p=0.95 for interaction). GLP-1 receptor agonists reduced major adverse cardiovascular events compared to placebo, with consistent benefits regardless of background SGLT2 inhibitor use (HR 0.78, 95% CI 0.49-1.24 with SGLT2i).
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