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Extended use isnt well-studied in humans, so most experts recommend cycling it, typically 48 weeks on, followed by a few weeks off, to support safety and effectiveness.

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In SYNJARDY or SYNJARDY XR-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin is dialyzable, with a clearance of up to 170 mL/minute under good hemodynamic conditions)

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You can read the full study in Nature here References Su, Q.J., Ashenhurst, J.R., Xu, W., Tran, V., Wu, R.R., Weldon, C.H., Shi, J., Hicks, B., 23andMe Research Team, Abul-Husn, N.S., Aslibekyan, S., Holmes, M.V., Koelsch, B.L