I haven't had ApoB checked yet but my cardiologist ordered it for my next panel in 6 weeks. I'll report back. He mentioned that ApoB is a better predictor of residual cardiovascular risk than LDL-C alone, especially when triglycerides are in play.
Excellent discussion. I want to emphasize one point for newer members reading this: the SELECT trial population was very specific — adults with established ASCVD and overweight/obesity but without type 2 diabetes. This was deliberate to isolate the CV benefit from any glucose-lowering confounding.
For those with T2DM, the evidence base goes back to SUSTAIN-6 (2016) and is now further supported by the SOUL trial. The totality of evidence across diabetic and non-diabetic populations is remarkably consistent.
If anyone has questions about how SELECT might apply to their specific clinical situation, please discuss with your treating physician. This is not medical advice — it's data interpretation.
This is incredibly helpful. I've been reading about GLP-1 agonists mainly in the context of weight loss and had no idea the cardiovascular data was this strong. The fact that the benefit appears independent of weight loss changes my understanding entirely.
Quick question: does the 20% MACE reduction apply equally to all three components (CV death, MI, stroke)? Or was one driving the result?
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Verify Your PeptidesGreat question. Here's the breakdown of SELECT's individual MACE components:
| Endpoint | Semaglutide | Placebo | HR (95% CI) |
|---|---|---|---|
| Primary MACE (composite) | 6.5% | 8.0% | 0.80 (0.72–0.90) |
| CV Death | 2.5% | 3.0% | 0.85 (0.71–1.01) |
| Nonfatal MI | 2.7% | 3.7% | 0.72 (0.61–0.85) |
| Nonfatal Stroke | 1.7% | 1.8% | 0.93 (0.74–1.15) |
The composite was driven primarily by the nonfatal MI reduction (HR 0.72), which was highly significant. CV death trended toward benefit but didn't reach statistical significance individually. Stroke reduction was modest and non-significant.
This pattern is actually very informative — MI reduction suggests plaque stabilization, which aligns with the anti-inflammatory hypothesis. The relatively smaller stroke effect may reflect different pathophysiology (more embolic vs. atherosclerotic in some populations).
One additional nuance worth noting: the SELECT population had a relatively low baseline event rate compared to older CVOT populations, which makes achieving a 20% relative risk reduction even more impressive. These were patients already on guideline-directed medical therapy — statins, antihypertensives, antiplatelets.
The absolute risk reduction was 1.5 percentage points over ~40 months. In an era where we celebrate 1-2% absolute risk reductions from adding ezetimibe or PCSK9 inhibitors to statins, this is substantial — especially from a single agent that simultaneously improves weight, blood pressure, lipids, and inflammation.
We may look back on SELECT as a landmark trial that redefined how we think about cardiometabolic risk management.