It's worth noting that, in the absence of pre-registration, one should should assume that the body of literature (and any systematic review or meta-analysis that relies on it) could be significantly influenced by the file drawer effect.
Anyway, I looked at a recent systematic review from those search results (https://pmc.ncbi.nlm.nih.gov/articles/PMC8622150/), and it found exactly one double-blind RCT (https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/) that seemed to support what the FDA is saying here. It had a fairly short duration (12 weeks) and a small cohort (48). I'm not medical expert but I do read medical literature as an amateur, and I'm pretty sure this is nowhere close to the standard of evidence for establishing safety and efficacy that the FDA used to demand. It feels like we may be reverting all the way back to the evidentiary standards that allowed crap like thalidomide onto the market.
