Commentary on the Results and Clinical Implications of the PROactive Study
- Robert Rizza, MD1,
- Robert Henry, MD2 and
- Richard Kahn, PHD3
- 1Mayo Clinic & Foundation, Rochester, Minnesota
- 2VA San Diego HealthCare System, San Diego, California
- 3American Diabetes Association, Alexandria, Virginia
- Address correspondence and reprint requests to Richard Kahn, PhD, American Diabetes Association, 1701 N. Beauregard St., Alexandria, VA 22311. E-mail: rkahn{at}diabetes.org
- CVD, cardiovascular disease
- PROactive, PROspective pioglitAzone Clinical Trial
- TZD, thiazolidinedione
Thiazolidinediones (TZDs), or glitazones, are a relatively new class of oral drugs that are used to treat type 2 diabetes (1–4). They lower blood glucose by targeting insulin resistance, one of the major underlying causes of the disease. In addition to their ability to lower blood glucose, TZDs also display a wide range of effects on lipids, blood pressure, weight, and other cardiovascular and metabolic risk factors. As with all other drugs, they can be associated with undesirable side effects.
By virtue of their glucose-lowering properties, all such agents will significantly reduce the risk of the microvascular complications associated with diabetes. On the other hand, no glucose-lowering agent has clearly been shown to significantly reduce macrovascular disease.
Since TZDs, in general, have a net favorable impact on blood lipid levels, may be associated with a reduction in blood pressure, and have positive effects on other physiological parameters associated with vascular disease (e.g., decreasing vascular inflammation, reducing insulin resistance), they have the potential to slow the progression of cardiovascular disease (CVD) in addition to lowering blood glucose.
Because of the above favorable actions of TZDs, the PROspective pioglitAzone Clinical Trial (PROactive) was initiated to assess the effects of pioglitazone (Actos; Takeda Pharmaceuticals and Eli Lilly) on the secondary prevention of macrovascular events in type 2 diabetic patients.
Study design
PROactive was a randomized, double-blind, placebo-controlled study in 5,238 patients with type 2 diabetes who were managed with diet and/or glucose-lowering medications and who had a history of macrovascular disease (5).
Male or female patients, aged 35–75 years, were randomized to receive placebo or pioglitazone titrated over 2 months to its maximally approved dosage (45 mg/day). Because study participants had preexisting CVD and diabetes of long duration (average 8 years), virtually all subjects at the time of enrollment were taking a …
