Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial.
The study suggests that higher doses of efpeglenatide may lead to better cardiovascular outcomes, but the clinical significance of lower doses remains uncertain.
Where it sits
this study against the rest of the efpeglenatide corpusSummary and findings
The study measured the effect of efpeglenatide doses (4 mg and 6 mg weekly) on major adverse cardiovascular events (MACE) in individuals with type 2 diabetes at high cardiovascular risk. A total of 125 participants in the placebo group experienced MACE, compared to 84 in the 6 mg group and 105 in the 4 mg group. The findings suggest a potential dose-response relationship in reducing MACE.
Abstract
<h4>Background</h4>In the AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes) cardiovascular outcomes trial, adding either 4 mg or 6 mg weekly of the glucagon-like peptide-1 receptor agonist efpeglenatide to usual care reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high cardiovascular risk. Whether these benefits are dose related remains uncertain.<h4>Methods</h4>Participants were randomly assigned in a 1:1:1 ratio to placebo, 4 mg or 6 mg of efpeglenatide. The effect of 6 mg versus placebo and of 4 mg versus placebo on MACE (a nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or unknown causes) and on all the secondary composite cardiovascular and kidney outcomes was assessed. A dose-response relationship was assessed using the log-rank test and χ<sup>2</sup> statistic for trend.<h4>Results</h4>During a median follow-up of 1.8 years, MACE occurred in 125 (9.2%) participants assigned to placebo, 84 (6.2%) participants assigned to 6 mg of efpeglenatide (hazard ratio [HR], 0.65 [95% CI, 0.5-0.86]; <i>P</i>=0.0027), and 105 (7.7%) assigned to 4 mg of efpeglenatide (HR, 0.82 [95% CI, 0.63-1.06]; <i>P</i>=0.14). Participants receiving high-dose efpeglenatide also experienced fewer secondary outcomes, including the composite of MACE, coronary revascularization, or hospitalization for unstable angina (HR, 0.73 for 6 mg, <i>P</i>=0.011; HR, 0.85 for 4 mg, <i>P</i>=0.17), a kidney composite outcome comprising sustained new macroalbuminuria, a ≥40% decline in estimated glomerular filtration rate or renal failure (HR, 0.63 for 6 mg, <i>P</i><0.0001; HR, 0.73 for 4 mg, <i>P</i>=0.0009), MACE or any death (HR, 0.67 for 6 mg, <i>P</i>=0.0021; HR, 0.81 for 4 mg, <i>P</i>=0.08), a kidney function outcome comprising a sustained ≥40% decline in estimated glomerular filtration rate, renal failure, or death (HR, 0.61 for 6 mg, <i>P</i>=0.0072; HR, 0.97 for 4 mg, <i>P</i>=0.83), and the composite of MACE, any death, heart failure hospitalization, or the kidney function outcome (HR, 0.63 for 6 mg, <i>P</i>=0.0002; HR, 0.81 for 4 mg, <i>P</i>=0.067). A clear dose-response was noted for all primary and secondary outcomes (all <i>P</i> for trend ≤0.018).<h4>Conclusions</h4>The graded salutary relationship between efpeglenatide dose and cardiovascular outcomes suggests that titrating efpeglenatide and potentially other glucagon-like peptide-1 receptor agonists to high doses may maximize their cardiovascular and renal benefits.<h4>Registration</h4>URL: https://www.<h4>Clinicaltrials</h4>gov; Unique identifier: NCT03496298.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.