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.
dan_philly said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 3 of 5 diagnostic criteria to meeting ZERO after 11 months of treatment.
dan_philly said:...we don't know the long-term effects of cardiovascular risk...
This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.
However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.
Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.
dan_philly said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 3 of 5 diagnostic criteria to meeting ZERO after 11 months of treatment.
Thank you — that is the clearest version of this I have read, and I have read a lot of them. I will report back once I have actually tried it.
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View ResultsFrom the other side of the consultation, briefly.
dan_philly said:...we're creating a generation dependent on cardiovascular risk...
I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?
Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.
If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. No action needed from anybody.