JACC took a deep dive into semaglutide’s cardiovascular impact, publishing six analyses of three separate trials that delivered new insights into the drug’s heart benefits, while raising even more questions about how it works.
One STEP-HFpEF trial analysis showed that patients with obesity-related HFpEF on semaglutide achieved cardiac remodeling benefits beyond the impact of weight loss.
- Semaglutide improved LA volume, LV diastolic function, and RV size, without affecting LV remodeling or LA mechanics.
- The LA volume benefits stemmed from weight loss, but improvements to LV diastolic function and RV size were due to semaglutide itself.
Another analysis of STEP-HFpEF suggested semaglutide decreases inflammation in patients with obesity-related HFpEF.
- Semaglutide decreased CRP, independent of weight loss or KCCQ-CSS and 6MWD improvements.
- While semaglutide decreased inflammation, it’s still unproven whether inflammation reduction leads to HF improvements.
The final STEP-HFpEF substudy found semaglutide to be especially effective at improving quality of life in patients with both AFib and obesity-related HFpEF.
- Semaglutide improved KCCQ-CSS scores, especially in patients with AFib.
- Reductions in CRP and weight were similar regardless of AFib status, suggesting semaglutide’s benefits in AFib/HFpEF patients go beyond inflammation and weight improvements.
Moving on to the SELECT trial, one substudy demonstrated semaglutide to be more effective in women for reducing inflammation and body mass.
- Women had greater weight loss and CRP reduction than men with semaglutide, but MACE and eGFR benefits were equal for both sexes.
- Even though weight loss and CRP reduction varied by sex, patient outcomes didn’t.
Another SELECT substudy found semaglutide significantly reduces COVID-related outcomes in patients with ASCVD and obesity.
- Semaglutide treatment reduced COVID-related mortality by 34% in people with ASCVD and obesity, while cutting serious adverse events (232 vs 277), although they couldn’t define the mechanisms of these reductions.
Finally, an analysis of the FLOW trial discovered semaglutide might both treat and prevent HF in patients with CKD and T2DM.
- Semaglutide decreased HF events and CV death by 27%, regardless of HF status, although how it did so was unclear.
The Takeaway
More than ever before, semaglutide seems like a wonder drug for weight-dependent heart conditions, but just how it works is still unclear. Even though there are plenty of drugs with unknown mechanisms of action, more research would help better define what drives semaglutide’s cardiovascular benefits.
