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Last updated Nov 29, 2025
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Chamath @ 01:17:19Inconclusive
health
Future GLP-1-based triple agonist drugs (e.g., Mounjaro and similar) will prove more effective at weight loss/metabolic improvement than the current generation of double-agonist GLP-1 drugs.
My key takeaway is that for many people, from a health perspective, I think that it it could be a really great solution. I think that these triple agonists that are coming out are going to be probably even more effective than these double agonists that we have right now.View on YouTube
Explanation

Evidence so far points in the direction Chamath predicted, but it’s still too early to say definitively.

  1. Current double‑agonist benchmark (tirzepatide/Mounjaro–Zepbound). In the SURMOUNT‑1 phase 3 trial, the dual GIP/GLP‑1 agonist tirzepatide produced up to about 22.5% mean weight loss at 72 weeks in people with obesity, and ~23% sustained loss at 3 years in longer‑term follow‑up. (investor.lilly.com)

  2. Triple‑agonist early results look numerically better. The leading triple agonist retatrutide (GLP‑1/GIP/glucagon) achieved up to 24.2% mean weight loss at 48 weeks in a phase 2 obesity trial, with broad improvements in cardiometabolic markers (blood pressure, lipids, HbA1c, liver fat). Multiple reviews describe this as the greatest weight loss reported in an obesity pharmacotherapy trial so far, and note that its average 17–24% loss in early studies exceeds that of currently approved drugs. (investor.lilly.com) Popular summaries similarly highlight that retatrutide’s ~24% loss appears higher than ~20–22% for tirzepatide and ~15% for semaglutide, while stressing the comparisons are across different trials. (menshealth.com)

  3. Why the prediction can’t be called fully right (yet).

    • No head‑to‑head outcome trials of a triple agonist vs tirzepatide have been completed; all comparisons are indirect across different study designs and durations.
    • Triple agonists remain investigational (phase 3 ongoing, no approvals as of late 2025), so long‑term safety, real‑world effectiveness, and cardiovascular/renal outcomes vs existing double agonists are unknown. (pubmed.ncbi.nlm.nih.gov)

Because the key triple‑agonist drugs are not yet approved and have not been directly compared to current double agonists in definitive phase 3 or real‑world settings, we cannot conclusively say they are more effective, even though early data are promising and directionally support Chamath’s view.