Skip to Main Content


Patients with type 2 diabetes mellitus (T2DM) are at increased risk of morbidity and mortality as a result of microvascular and macrovascular complications. Such complications are proposed to be induced by a hyperglycemic-mediated imbalance between protective and toxic factors resulting in damage to the vasculature.1 Prevention of hyperglycemia, delay of progression to impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), and eventually development of impaired insulin secretion and insulin resistance are popular topics for research due to the high risk of complications associated with diabetes. The Diabetes Prevention Program (DPP) and the Diabetes Prevention Study (DPS) showed that effective use of lifestyle modifications decreased the risk of diabetes in high risk patients.2,3 The DPP also found that metformin reduced the risk of developing diabetes in patients with impaired glucose tolerance by 31%.2 Several studies using thiazolidinediones (TZDs) showed they might be effective in significantly delaying or preventing progression of IGT to T2DM, as well as, reducing the risk of secondary macrovascular events in high-risk patients.4,5 


Recently, DeFronzo and colleagues examined whether pioglitazone could reduce the risk of T2DM in adults with IGT in the ACT NOW (Actos Now for the prevention of diabetes) study. They conducted a randomized, double-blind, placebo-controlled study with a total of 602 patients. The patients received either placebo or pioglitazone (30 mg for 1 month, then increased to 45 mg). The primary endpoint was the development of T2DM (see Table). The diagnosis of diabetes was confirmed by an annual oral glucose-tolerance test. The study included men and women, 18 years of age and older of all ethnic groups who had impaired glucose tolerance (see Table), a fasting plasma glucose (FPG) level between 95-125 mg/dL, a body-mass index (BMI) ≥ 25 kg/m2 and at least one other risk factor for diabetes. Exclusion criteria were subjects with diabetes mellitus; previous treatment with TZD (ever) or metformin (within one year prior to randomization), previous treatment with a sulfonylurea, meglitinide, alpha glucosidase inhibitor, or insulin (for more than one week within the last year or within 3 months prior to randomization), and medical conditions associated with an increased risk of intervention or decreased life span. Participants of the study returned every 2 months during the first year and once every 3 months thereafter. Weight, blood pressure, pulse, FPG, and edema were measured at each visit. An increase in edema was defined as an increase of two grades or more from baseline. HbA1c, alanine aminotransferase and aspartate aminotransferase levels were measured every 6 months. An oral glucose-tolerance test was performed annually and all baseline measurements were repeated at the end of the study. The median follow-up period was 2.4 years. Of the 161 subjects that did not complete the study, 12 were due to weight gain (9 in pioglitazone group and 3 in placebo group) and the remaining due to reasons not related to the study. The median follow up for this group was ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.