Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes (PROactive)

Inclusion Criteria

• Type 2 diabetes mellitus
• Glycosylated hemoglobin above the upper limit of normal (ie, the local equivalent of 6.5% for)

• Established history of macrovascular disease, defined as 1 or more of:

  • Myocardial infarction at least 6 months before entry into the study.
  • Stroke at least 6 months before entry into the study
  • Percutaneous coronary intervention or coronary artery bypass graft at least 6 months before entry into the study.
  • Acute coronary syndrome at least 3 months before entry into the study.
  • Objective evidence of coronary artery disease.
  • Peripheral arterial obstructive disease

Exclusion Criteria

• Signs of type 1 diabetes.
• Patients prescribed insulin as sole therapy for glycemic control of diabetes for 2 weeks or more at any time in the previous 3 months.
• Myocardial infarction, stroke, coronary artery bypass graft, or percutaneous cardiac intervention in the 6 months prior to enrolment.
• Acute coronary syndrome in the 3 months prior to enrolment.
• Heart failure at entry defined as patient having a New York Heart Association functional score of II or above.
• Had an appointment for a coronary angiogram or endovascular or surgical intervention.
• Leg ulcers, gangrene, or ischemic rest pain.
• Had an appointment for an angiogram or endovascular or surgical intervention for leg ischemia.
• Had undergone a major operation (defined as a surgical procedure lasting for more than 30 minutes) at any time in the previous 4 weeks.
• Significantly impaired hepatic function, defined as alanine aminotransferase greater than 2.5 times the upper limit of normal.
• Familial polyposis coli.
• Required dialysis.
• History of alcohol or drug abuse.
• Any other intercurrent disease believed to be likely to have a significant impact on the patient's life expectancy during the course of the study (eg, cancer).
• Patient was undergoing follow-up as part of another clinical trial or less than 3 months had elapsed since the last dose of an investigational drug or procedure.
• Hypersensitivity to pioglitazone or other TZD.
• Current use of pioglitazone or other TZD.
• Patient was known to be infected with human immunodeficiency virus or was known to have viral hepatitis.
• Women who were any of the following: pregnant, breast feeding, wished to become pregnant during the course of the study or of childbearing potential and not planning to use a reliable method of contraception throughout the study.