Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
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.
Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
What I am trying to establish is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. Happy to be told the question itself is wrong.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
PharmHunterJen 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…
Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol entirely! My cardiologist is thrilled.
If you're on BP meds and losing weight on a GLP-1, monitor your BP at home regularly. Hypotension symptoms (dizziness, lightheadedness when standing) mean your BP meds may need reduction. Don't wait for your next scheduled appointment — call your doctor.
PharmHunterJen 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…
I read this differently from PharmHunterJen, on substance rather than tone. 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.
Janoshik Analytical — Independent Testing
Trusted third-party HPLC & mass spectrometry analysis. Verify peptide purity with the lab the community relies on. Independent. Accurate. Transparent.
Verify Your PeptidesGL Biochem (Shanghai) Ltd. — Direct Manufacturer
Est. 1998. The synthesis house behind the vials you send for testing. ISO 9001 and cGMP certified, 1,500+ staff, batch-specific COA with every order.
Browse GL BiochemDanielChem_CHI said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated with lower BMI also show associations with reduced cardiovascular risk, confirming a causal pathway[1].
This "natural experiment" (people born with genetically higher GLP-1 signaling being leaner and healthier) provides orthogonal evidence supporting the pharmacological approach. When genetic epidemiology, clinical trials, and mechanistic studies all converge, confidence in the therapeutic approach is high.
[1] Zheng SL, et al. Lancet Diabetes Endocrinol. 2023;11(12):869-879.
TrialNerd_Beth said:Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off metoprolol entirely!
This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.