[en] Administration, Oral ; Cardiovascular Diseases/etiology/prevention & control ; Diabetes Mellitus, Type 2/complications/drug therapy ; Humans ; Hypoglycemic Agents/administration & dosage/therapeutic use ; Insulin/therapeutic use ; Placebos ; Risk Factors ; Thiazolidinediones/administration & dosage/therapeutic use
[en] PROactive is a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. Patients were assigned to oral pioglitazone titrated from 15 mg to 45 mg or matching placebo, to be taken in addition to their glucose-lowering drugs and other medications. After a mean follow up of 34.5 months, pioglitazone reduced the composite of all-cause mortality, non-fatal myocardial infarction, and stroke (intention to treat analysis: hazard ratio = 0.84; 95% CI: 0.72-0.98; p = 0.027). Various favourable metabolic effects could contribute to this cardiovascular protection, i.e. an absolute 0.5 % reduction in HbA1c, a 9% increase in HDL cholesterol, a 13% decline of triglycerides, and a 3 mm Hg reduction in systolic blood pressure in the pioglitazone group compared to placebo. The requirement of insulin was reduced by almost 50% in the pioglitazone group as compared to the placebo group. The incidence of cases of oedema and congestive heart failure was higher in the pioglitazone group. In conclusion, in patients with type 2 diabetes who are at high cardiovascular risk, pioglitazone improves cardiovascular outcome, and reduces the need to add insulin to glucose-lowering regimens compared to placebo.