My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
What I am after is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
steve_okc said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Metabolic syndrome resolution on cardiovascular risk: I went from meeting 4 of 5 diagnostic criteria to meeting ZERO after 9 months of treatment.
The 5 criteria (and my journey):
- Waist circumference: 48" → 36" ✅ Resolved
- Triglycerides: 226 → 116 ✅ Resolved
- HDL: 32 → 58 ✅ Resolved
- Blood pressure: 146/92 → 119/73 ✅ Resolved
- Fasting glucose: 121 → 84 ✅ Resolved
Metabolic syndrome reversal is, in my view, the most medically significant outcome of GLP-1 therapy.
anders_CPH said:Metabolic syndrome resolution on cardiovascular risk: I went from meeting 4 of 5 diagnostic criteria to meeting ZERO after 9 months of treatment.
anders_CPH 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.
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Browse GL Biochemsteve_okc said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
This matches mine closely enough to be worth saying so out loud.
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.