Summary
The June 2021 AMPLITUDE-O study evaluated the use of efpeglenatide in patients with type 2 diabetes mellitus who had either a history of cardiovascular (CV) disease or current kidney disease plus one additional CV risk factor. This randomized controlled trial evaluated CV risk reduction in patients taking weekly subcutaneous injections of efpeglenatide, a novel exendin-based glucagon-like peptide-1 receptor agonist (GLP-1 RA).1 Prior studies established CV risk reduction properties of analogs to human GLP-1;2 however, a dedicated outcomes trial of another exendin-based molecule (exenatide once weekly) did not demonstrate CV benefit,3 which raised concerns that the CV benefit from GLP-1-based therapies was not a class effect.
The results showed a significant reduction in the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, as well as a key secondary composite renal outcome. However, gastrointestinal side effects were more common with efpeglenatide. The CV and renal outcomes were independent of baseline renal function or use of metformin or sodium-glucose cotransporter-2 inhibitors. The benefits of this novel GLP-1 RA are consistent with other agents in the class.
Sources
1Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896-907. doi:10.1056/NEJMoa2108269.
2Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322. doi:10.1056/NEJMoa1603827.
3Holman RR, Bethel MA, Mentz RJ, et al; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228-1239. doi: 10.1056/NEJMoa1612917.