In CV disease, GLP-1 RAs and SGLT2 inhibitors reduce CV mortality
The results of the meta-analysis support recommendations to use sodium-glucose cotransporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in diabetes patients who have or are at high risk for cardiovascular (CV) disease, an ACP Journal Club commentary said.
A network meta-analysis looked at the effects of dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with established cardiovascular (CV) disease. It pooled data from 20 studies with 129,465 participants and found that GLP-1 RAs and SGLT2 inhibitors were likely to reduce the risk of death from CV disease or any cause, SGLT2 inhibitors were likely to reduce risk of hospitalization for heart failure, and GLP-1 RAs may reduce fatal and nonfatal stroke.
The study was published online in the Cochrane Database of Systematic Reviews on Oct. 25, 2021. The following commentary by Michelle D. Kelsey, MD, and L. Kristin Newby, MD, MHS, was published in the ACP Journal Club section of Annals of Internal Medicine on March 1.
The systematic review and meta-analysis by Kanie and colleagues compared the benefits and harms of 3 novel antihyperglycemic agents for patients with established CV disease (most patients also had type 2 diabetes mellitus). Results are consistent with those of other meta-analyses, which showed that both GLP-1 RAs and SGLT2 inhibitors reduce CV mortality, GLP-1 RAs reduce stroke, and SGLT2 inhibitors reduce heart failure hospitalization. The meta-analysis also confirms the known neutral CV effects of DPP4 inhibitors and lack of benefit of GLP-1 RAs in heart failure.
Network meta-analyses such as this can be used to compare agents that have not been tested against each other directly. As with pairwise meta-analyses, network meta-analyses are subject to bias due to heterogeneity between studies. Network meta-analyses also introduce additional bias due to inconsistencies in comparators across different studies. Reassuringly, the results of the network meta-analysis by Kanie and colleagues were largely consistent with pairwise data, as are other network meta-analyses of the novel antihyperglycemic agents.
These results strengthen the expert consensus recommendations from the American College of Cardiology, which support the use of SGLT2 inhibitors or GLP-1 RAs in patients with diabetes who also have, or are at high risk for, CV disease. Although this review focused specifically on patients with established disease, many of the included CV outcomes trials also included patients with CV risk factors, supporting use of these drugs in this primary prevention population as well.