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Caruso, Irene; Cignarelli, Angelo; Giorgino, Francesco
Trends in endocrinology and metabolism, September 2019, 2019-09-00, 20190901, Letnik: 30, Številka: 9Journal Article
The latest recommendations from the American Diabetes Association and the European Association for the Study of Diabetes prioritize the use of drugs with proven cardiovascular (CV) benefit in patients with established CV disease. Especially among the glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RA) class, results of cardiovascular outcomes trials (CVOT) have been heterogeneous. Baseline characteristics of the population, study design, drugs in the control arm, modifications of CV risk factors, including glycemic control, reduction of hypoglycemia, and the GLP-1RA direct effects on CV cells and tissues, were considered. Ultimately, the time of exposure to the GLP-1RA appears to be the factor most prominently explaining trial heterogeneity. Thus, the CV benefit should be regarded as a class effect of GLP-1RA, as largely similar results are seen for drugs sharing a common mechanism of action. ELIXA was the only GLP-1RA CVOT that failed to show any CV benefit over usual care. In LEADER, SUSTAIN-6, HARMONY Outcomes, and REWIND, GLP-1RA showed statistical superiority on MACEs compared to usual care, while EXSCEL (P=0.06) just grazed it and PIONEER 6 showed a nonsignificant 21% reduction (P=0.17). However, SUSTAIN-6 lacked a prespecified analysis for superiority.Dulaglutide significantly decreased the incidence of MACEs by 12% in a population at a lower CV risk compared to previous CVOT.Although GLP-1RA CVOT were not powered to detect such differences, GLP-1RA seemed to affect the individual MACE components according to specific patterns: liraglutide and oral semaglutide produced significant reductions of CV death; subcutaneous semaglutide and dulaglutide promoted a significant decrease in non-fatal stroke; albiglutide largely reduced non-fatal MI; and exenatide LAR did not show a significant effect in any component.
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