Dr.GastroMayo said:SUSTAIN-6 was the first CVOT to show cardiovascular benefit with semaglutide, relevant to cardiovascular risk.
I read this differently from Dr.GastroMayo, 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.
chris_chi24 said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
chris_chi24 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.
PeptideChemSF said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
I'm 67 years old and want to share my perspective on cardiovascular risk as an older member of this community.
My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.
17 months later: down 44 lbs, off lisinopril, A1C from 8.8% to 5.5%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.
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View ResultsFollowing on from robert_kc — and this may be the naive question:
What did you change at the same time, and can you separate the two now?
newstart_MO said:I'm 67 years old and want to share my perspective on cardiovascular risk as an older member of this community.
Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].
Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.
These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.