Aim: Metformin has recently been considered as a possible pharmacological complement to lifestyle measures for preventing type 2 diabetes in high-risk subjects. However, little is known of its effects on metabolic and cardiovascular risk factors in non-diabetic subjects.
Methods: The BIGPRO1 trial was a 1-year multicentre, randomized, double-blind, controlled clinical trial of metformin versus placebo, carried out in the early 1990s, in 457 upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin. We compared the changes (1-year minus baseline) in cardiometabolic risk factors between treatment groups in two subsets of trial subjects: those with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=101); and those who fulfilled the inclusion criteria of the Diabetes Prevention Program (DPP) (n=51). Comparisons were adjusted for age and gender.
Results: In the IFG/IGT subset, significant differences in 1-year changes were observed for systolic blood pressure, which decreased markedly more in the metformin group than in the placebo group (P<0.003), and for fasting plasma glucose, and total and LDL cholesterol, which decreased slightly in the metformin group, but increased in the placebo group (P<0.04). Similar results were observed in the subset with DPP criteria. Also, there were no significant differences in 1-year changes for weight, waist-to-hip ratio, 2-h post-load blood glucose, fasting and 2-h post-load insulin, HDL cholesterol, triglycerides and fibrinolytic markers between the two treatment groups.
Conclusion: In subjects at high risk of developing diabetes, the use of metformin showed beneficial and no untoward effects on cardiometabolic risk factors.