Dr.SleepRoch said:Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated…
This is where I part company with the consensus forming above. 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.
Dr.ObesityMed said:Prescribed on cardiovascular grounds rather than for weight, and almost everything written for patients assumes the opposite.
Dr.ObesityMed said:...cardiovascular risk is just another fad...
I understand the skepticism — we've all seen "miracle" weight loss solutions come and go. But consider what makes GLP-1 agonists different:
- Phase 3 RCTs with thousands of participants (not 20-person pilot studies)
- Published in NEJM, JAMA, Lancet (not press releases)
- Replicated across multiple independent research groups
- Proven cardiovascular and renal benefits beyond weight loss
- Biological mechanism fully characterized at the receptor level
This isn't a fad — it's a new drug class supported by the highest level of clinical evidence. The comparison to past fads is understandable but inappropriate.
JennaRN said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
I want to bring up the cardiovascular angle on cardiovascular risk.
The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.
For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
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View ResultsOne thing that is still open after Dr.LeslieOBGYN’s answer:
Was that from a primary source or from a summary of one?
PharmD_Rodriguez said:I want to bring up the cardiovascular angle on cardiovascular risk.
I'm 58 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.
11 months later: down 58 lbs, off atorvastatin, A1C from 7.6% to 5.5%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.