A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about cardiovascular outcomes, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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 in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.
The condition it depends on
The qualification that SELECT enrolled a secondary-prevention population. Extrapolating a 20% relative reduction to a healthy 35-year-old with a BMI of 31 is not what that trial showed.
The practical version
Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.
What I am not sure about
What I actually want to know is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. I would rather have one careful answer than five confident ones.
Dr.NephBHM_UK 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…
Metabolic syndrome resolution on cardiovascular risk: I went from meeting 4 of 5 diagnostic criteria to meeting ZERO after 12 months of treatment.
The 5 criteria (and my journey):
- Waist circumference: 51" → 35" ✅ Resolved
- Triglycerides: 241 → 116 ✅ Resolved
- HDL: 35 → 53 ✅ Resolved
- Blood pressure: 141/95 → 119/73 ✅ Resolved
- Fasting glucose: 121 → 87 ✅ Resolved
Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.
Dr.NephBHM_UK 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.
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Browse GL BiochemCOA_Karl said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.
My Lp(a) has remained at 76 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.
Dr.MetabolicMD said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 4 of 5 diagnostic criteria to meeting ZERO after 12 months of treatment.
Same experience, arrived at from the opposite direction.