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Eurich et al note that observational data from Reduction of Atherothrombosis for Continued Health (REACH) that we published in the Archives1 complement previous studies, and they fear that obtaining a higher level of proof regarding the safety and perhaps the benefits of metformin in very high-risk patients is not achievable.
Roussel R, Bhatt DL, Steg PG, . Levels of Evidence Needed for Changing Indications, Contraindications, and Food and Drug Administration Labeling: The Case of Metformin—Reply. Arch Intern Med. 2011;171(11):1042-1043. doi:10.1001/archinternmed.2011.225