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

Abstract

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.

Clinical Profile and Management of Patient Patients with Ischemic Heart Disease and/or Peripheral Artery Disease in Clinical Practice: The APALUSA Study

“…In fact, our study showed that the modification of antidiabetic treatment in this population was insufficient. Despite the benefits that these drugs have demonstrated in clinical trials, their use in clinical practice remains markedly low [ 37 , 38 ].…”

Comprehensive Cardiovascular and Renal Protection in Patients with Type 2 Diabetes

“…In fact, a meta-analysis of randomized clinical trials that included the UKPDS concluded that metformin has a neutral effect on the incidence of myocardial infarction and CV or all-cause morbidity and mortality [ 48 ]. On the other hand, although in studies of CV safety with GLP-1 receptor agonists or SGLT2i 75% of patients were on treatment with metformin, the CV and renal benefit was also seen in the subgroup of patients that were not taking this drug, suggesting that the cardio- and nephroprotective effect of these drugs was independent of concomitant treatment with metformin [ 146 , 147 , 148 ].…”

Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications

“…A number of trials have shown significant reductions in major CV events after treatment with GLP-1 receptor agonists [ 152 , 153 , 154 , 155 ]. These results were further supported by a recent meta-analysis, in which GLP-1 receptor agonist treatment reduced major adverse CV events (MACE) by 12% [ 156 ].…”