Abstract 16290: Characterization of Heart Rate Increases With Glucagon-Like Peptide-1 Agonist Therapy
Objective: Clinical trial data suggest glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be associated with increased heart rate (HR) in patients (pts) with type 2 diabetes; the clinical significance of this is unknown. To better characterize HR changes with exenatide and other antihyperglycemics, we examined HR increases in trials of exenatide once weekly (EQW), including in pts with major adverse CV events (MACE).
Methods: A post-hoc analysis pooled vital sign data from 11 studies lasting 12-30 weeks of EQW (N=2096) vs placebo (PBO; N=23), exenatide twice daily (EBID, N=606), liraglutide (LIRA; N=450), insulin (INS; N=540), metformin (MET; N=246), sitagliptin (SITA; N=329) or pioglitazone (PIO; N=328). For the analysis, pts were a priori stratified by baseline (BL) HR (≤60 [4%], >60-≤90 [92%] and >90 bpm [4%]). HR change categories were defined in 5 bpm intervals up to >20 bpm, a potential CV risk factor. The relationship of continuous HR change with BL HR was examined. Unadjudicated MACE was defined using Standardized MedDRA Queries (Broad) for myocardial infarction, CNS hemorrhages and cerebrovascular accidents, and any cardiac death.
Results: Variability in HR over time was observed for all treatments: increases appeared numerically greater with EQW and LIRA. In pts with BL HR >60-≤90 bpm, mean±SD endpoint HR changes were: EQW, +2.8±8.5; LIRA, +2.6±7.6; EBID, +0.9±7.9; PBO, +0.6±7.9; SITA, -0.0±7.4; MET, -0.5±8.0; INS, -0.6±8.1; PIO, -1.1±7.8 bpm. In each treatment group, 44%-64% of pts had an HR increase of >5-≤20 bpm at ≥1 visit. Most pts (92%) had no HR changes >20 bpm. In those who did, changes did not seem sustained: only 0.3% of pts had ≥4 visits with HR changes >20 bpm. In all treatment groups, most pts with increased HR were in the lowest BL HR stratum. HR change and BL HR were negatively correlated (P<0.0001) for all active therapies, including EQW (r=-0.37). MACE risk was low (<1% had events), not different between treatments, and not more common in patients with repeated HR changes >20 bpm in the overall pt population or EQW recipients.
Conclusion: HR increases occurred with all treatments including GLP-1 RAs. HR increases were correlated with BL HR and most notable in pts with BL HR ≤60 bpm. No clear association between increased HR and MACE was found.
- © 2013 by American Heart Association, Inc.