Heart rate increase on GLP-1 — need advice

wei_SG said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.

Compare to established therapies:

These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.

wei_SG said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

CarlaRPh_TPA said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].

Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.

These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.

julia.endo said:

NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).

Adding a me-too, because a thread of one person's experience is not much use.