NeuroNate said:The glucagon component looks paradoxical and is not.
Pushing back on NeuroNate here. 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.
One concrete data point for the thread. For anyone tracking the class: GLP-1 alone gets you appetite, GLP-1 plus GIP adds tolerability and lipid handling, and adding glucagon adds expenditure and liver-fat reduction. Each addition also adds a receptor system that can generate side effects.
KevinCompounds said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
KevinCompounds 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.
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Browse GL BiochemFollowing on from Dr.PainCLE — and this may be the naive question:
What the phase 2 dropout pattern implies about how the phase 3 tolerability will read?
Closing the loop on my own question.
Rereading it with the dropout table open changed my view. I still think it is the most interesting molecule in the pipeline; I no longer think the 24% is the number that will end up on a label.