Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110–125 vs. 100–109 mg/dL (6.1–6.9 vs. 5.6–6.0 mmol/L) and A1C levels 6.0–6.4% (42–46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes—i.e., those with FPG concentrations of 110–125 mg/dL (6.1–6.9 mmol/L) or A1C levels of 6.0–6.4% (42–46 mmol/mol) or women with a history of gestational diabetes mellitus—should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.

Metformin Should Not Be Used to Treat Prediabetes — Diabetes Care 2020 Sep; 43(9): 1983-1987. https://doi.org/10.2337/dc19-2221