Giovanni Antonio Silverii

Aims Whether to recommend specifically the glucose‐lowering therapies with cardiovascular benefit only in secondary prevention, or also in patients with multiple risk factors (MRF) but without established atherosclerotic cardiovascular disease (ASCVD), is controversial across the guidelines for diabetes. Materials and Methods We performed a meta‐analysis of clinical trials with major adverse cardiovascular events (MACE) as an outcome. Results The definitions of ASCVD and MRF were heterogeneous across trials; nevertheless, the incidence of MACE was 2.8‐fold higher in people with ASCVD in trials with sodium‐glucose cotransporter 2 inhibitors (SGLT2is), and 3.9‐fold in trials with glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA). Both SGLT2i and GLP‐1 RA were associated with a significant reduction in the incidence of MACE in people with previous ASCVD [inverse variance‐odds ratio 0.91, 95% confidence interval (0.86: 0.97) for SGLT2i, Mantel‐Haenszel odds ratio 0.85, 95% confidence interval (0.81: 0.90) for GLP‐1 RA], whereas no significant reduction was detected in those without; on the other hand, no significant difference in effect was found between the two groups as well. The sample of patients without ASCVD enrolled in clinical trials is insufficient to draw reliable conclusions in this population; however, even assuming the same benefit detected in people with ASCVD also in those with MRF, the number needed to treat would differ (35 for secondary, 99 for primary prevention of a MACE with a SGLT2i; 21 for secondary, 82 for primary prevention with a GLP‐1 RA, respectively), given the difference in absolute cardiovascular risk at baseline. Conclusion The distinction between patients with ASCVD and those without ASCVD and MRF appears therefore justified by available evidence.