Response to Comment on Pasanisi et al. Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial. Diabetes Care 2025;48:265–272 Free

The comment by Davidson (1) points attention to an important issue regarding our article (2), which was recently published in Diabetes Care, namely, the definition of prevention. The observation of Davidson is correct, because the role of metformin is to treat dysglycemia (both impaired fasting glycemia and impaired glucose tolerance). This comment gives us the opportunity to show our results in more detail. In people with baseline plasma glucose ≥110 mg/dL, the hazard ratio (HR) of type 2 diabetes in the metformin-treated (MET) groups was 0.16 (95% CI 0.07–0.40), based on 42 cases of diabetes. In people with baseline plasma glucose ≥100 and <110 mg/dL, the HR of type 2 diabetes in the MET groups was 0.09 (95% CI 0.01–0.69), based on 12 cases of diabetes. In people with baseline plasma glucose <100 mg/dL, the HR of type 2 diabetes in the MET groups was 0.94 (95% CI 0.06–15.2), based on 2 cases of diabetes. According to the World Health Organization, prevention is defined as actions to reduce the risk of disease or disability or to slow the progression of a disorder (3). In our view, if metformin reduces the occurrence of the clinical diagnosis of diabetes, this delay means prevention.

As for the second point, our sentence was ambiguous. The correct sentence should have been “With the same dose of MET as in the MeMeMe, the DPP trial reduced the incidence of diabetes by 31%, and a small but significant long-term reduction of glycosylated hemoglobin persisted after 21 years of follow-up” (4).