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The unfortunate truth is that big risk signals (lets say the kind you get from drinking antifreeze) can be spotted from the anecdotal experience of people in the world just trying things, but small-but-serious risk signals (lets say cardiovascular disease with tofacitinib) are really hard to identify without a proper trial or a proper observational study

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Holzheimer RG, Steinmetz W

Glucagon receptor activation is minimal at 1-2mg but increases significantly at 4mg and becomes a major driver of the metabolic profile at 8mg and above

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