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
Substituting red meat with high-quality plant protein sources was associated with more favorable changes in cardiovascular risk factors relative to dietary replacements combined in a recent meta-analysis of randomized clinical trials (RCTs) published in Circulation.
CONCLUSIONS – Metformin reduces the development of diabetes over 15 years. The subsets that benefitted the most include subjects with higher baseline fasting glucose or HbA1c and women with a history of GDM.
You can access the abstract and full study online at this link to the Diabetes Journal.
The commentary article at this link is also an interesting read.
More Evidence for a Prevention-Related Indication for Metformin: Let the Arguments Resume!
According to some reports metformin poisoning, though rare, is associated with a mortality rate of 30%.
In a retrospective study, diabetic patients who were taking metformin had worse cognitive performance than those not taking the drug (odds ratio 2.23, 95% CI 1.05-4.75), Eileen Moore, PhD, of the University of Melbourne in Australia, and colleagues reported online in Diabetes Care.
Additionally, patients with diabetes who had vitamin B12 levels less than 250 pmol/L also had worse cognitive performance (OR 2.29, 95% CI 1.12-4.66), and the association between metformin and cognitive impairment was weakened after adjusting for vitamin B12 levels, they stated.
A large, multicenter trial found a 24% reduced risk of all-cause mortality among patients on the drug, compared with those not taking it, according to Ronan Roussel, MD, PhD, of Groupe Hospitalier Bichat-Claude Bernard in Paris, and colleagues.