In a recent meta-analysis, in patients with heart failure with mildly reduced and preserved ejection fraction, most of whom had overweight or obesity, form STEP-HFpEF, STEP-HFpEF DM, and patients with investigator-reported history of heart failure with mildly reduced and preserved ejection fraction form SELECT and FLOW trials with semaglutide 2.4 mg in the first 3 and 1.0 mg in the last trial, semaglutide reduced the combined endpoint of cardiovascular death or worsening of heart failure events combined (hazard ratio 0.69, 95% CI: 0.530.89) and worsening heart failure alone (hazard ratio 0.59 95% CI: 0.410.82) compared to placebo, while there was no significant effect on reduction of cardiovascular death alone [81]
For 5-amino-1MQ specifically: Preclinical studies have not prominently described heart rate elevation as a dominant signal The mechanism (NNMT inhibition, NAD+ preservation) does not have the same direct cardiac implications as nuclear receptor agonism Human cardiovascular data at clinically relevant exposures are limited For physicians, the current evidence base does not support a major cardiovascular safety flag, but the limited human dataset means confident statements are premature
HSS Journal , 2025
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Has it been studied in humans
