Antidiabetic combination therapy and cardiovascular outcomes: An evidence-based approach
Abstract
Type 2 diabetes mellitus is associated with a 2-4 times increased risk of cardiovascular (CV) disease. Glucagon-like polypeptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are two important classes of drugs with CV benefits independent of their antihyperglycemic efficacy. The CV outcome trials of both GLP1RA and SGLT2i have demonstrated CV superiority/neutrality concerning major adverse CV events (MACE). While GLP1RAs have exhibited a significant reduction in ischemic stroke and myocardial infarction (MI), SGLT2i have demonstrated a uniformly significant reduction in hospitalization for heart failure (HF) as a class effect. The unique clinical benefits and the distinct but complementary mechanisms of action make the combination of these drugs a mechanistically sound one. Recent meta-analyses suggest an independent and additive benefit of combination therapy of GLP1RA/SGLT2i vs monotherapy. Zhu et al, in a recent issue of the World Journal of Diabetes, demonstrates a numerically lower hazard ratio (HR) for CV outcomes with combination therapy vs monotherapy with either agent, with a reduction in MACE compared to GLP1RA alone [HR = 0.51, 95% confidence interval (CI): 0.16-1.65], or SGLT2i alone (HR = 0.48, 95%CI: 0.15-1.54). The CV death rate was also lower with combination therapy compared to GLP1RA alone (HR = 0.58, 95%CI: 0.08-3.39), or SGLT2i alone (HR = 0.55, 95%CI: 0.07-3.25). Fatal and non-fatal MI and fatal and non-fatal stroke…
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