Dr.EndoIndy said:Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five.
This answered a question I did not know how to ask. Printing the relevant bit and taking it with me.
From the other side of the consultation, briefly.
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.
Dr.DermMIA said:SURMOUNT-1 landed around 20.9% mean weight loss at 15mg over 72 weeks, against roughly 15% for semaglutide 2.4mg in STEP 1.
I read this differently from Dr.DermMIA, on substance rather than tone. The "tirzepatide is simply better" summary irritates me. It is better on mean weight loss, and the cardiovascular outcome evidence is far thinner than semaglutide's. If the reason for treating is cardiovascular risk rather than weight, the evidence base points the other way.
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View ResultsDr.RaviCardio 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…
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 64 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.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Tagging this one for the weekly digest.