Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program

This review describes the effect of lifestyle change or metformin compared with standard care on incident type 2 diabetes and cardiometabolic risk factors in the Diabetes Prevention Program and its Outcome Study. The Diabetes Prevention Program was a randomized controlled clinical trial of intensive lifestyle and metformin treatments versus standard care in 3234 subjects at high risk for type 2 diabetes. At baseline, hypertension was present in 28% of subjects, and 53% had metabolic syndrome with considerable variation in risk factors by age, sex, and race. Over 2.8 years, type 2 diabetes incidence fell by 58% and 31% in the lifestyle and metformin groups, respectively, and metabolic syndrome prevalence fell by one-third with lifestyle change but was not reduced by metformin. In placebo- and metformin-treated subjects, the prevalence of hypertension and dyslipidemia increased during the Diabetes Prevention Program, whereas lifestyle intervention slowed these increases significantly. During long-term follow-up using modified interventions, type 2 diabetes incidence decreased to ≈5% per year in all groups. This was accompanied by significant improvement in cardiovascular disease risk factors over time in all treatment groups, in part associated with increasing use of lipid-lowering and antihypertensive medications. Thus a program of lifestyle change significantly reduced type 2 diabetes incidence and metabolic syndrome prevalence in subjects at high risk for type 2 diabetes. Metformin had more modest effects.