SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose‐lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review.

Objectives: To assess the efficacy of glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) and sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, administered without metformin on cardiovascular outcomes in type 2 diabetes patients. Methods: A systematic review was performed according to Cochrane's methodological standards. We included randomized clinical trials (RCTs) on adult type 2 diabetes patients, assessing the efficacy of SGLT2 inhibitors and GLP1‐RAs compared to other glucose‐lowering drugs and/or RCTs that presented data of a subgroup of type 2 diabetes patients without metformin use at baseline. The main outcome was the reduction of the risk of any major adverse cardiovascular events (MACE) reported individually or as a composite outcome. Results: Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta‐analysis. Three of these studies assessed the efficacy of GLP1‐RAs and two of SGLT2 inhibitors. In patients without metformin at baseline, GLP1‐RAs in comparison with placebo reduced the risk of MACE significantly by 20% (HR: 0.80; 95% CI: 0.71–0.89). SGLT2 inhibitors also significantly reduced the risk of MACE by 32% (HR: 0.68; 95% CI: 0.57–0.81). Conclusions: SGLT2 inhibitors and GLP1‐RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events. [ABSTRACT FROM AUTHOR]