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Nevertheless, use of metformin may decrease vitamin B 12 status: a meta-analysis of four short-term intervention trials (up to 4 months duration) in patients with type 2 diabetes found that metformin use decreased serum cobalamin concentrations by 57 pmol/L, which could have clinical implications if such patients have suboptimal vitamin B 12 status (146)

Even safety data on TB-500 (synthetic TB4) is relatively scarce, with only a few studies reporting the potential side effects of its systemic application: In a 2010 study in 10 participants, TB4 caused occasional mild to moderate symptoms like headache and dizziness but no serious reactions or toxicities, even at doses up to 1260mg, administered daily for up to two weeks