Pioglitazone improved lipid profiles in type 2 diabetes

The agent was given in addition to standard therapies for glucose management and cholesterol.

Issue: November 2006

Treatment with metformin, sulfonylurea or insulin did not mitigate the improvements in lipid profiles observed among patients with type 2 diabetes who were taking pioglitazone.

Pioglitazone (Actos, Takeda) is a PPAR-gamma agonist and has been previously shown to improve triglyceride and HDL levels.

The PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) trial was designed to observe the effects of pioglitazone on mortality and macrovascular morbidity in a high-risk group of patients with type 2 diabetes.

Patients were randomized to either pioglitazone or placebo. “Importantly, these patients were continued on all existing therapy including diet, glucose-lowering agents, antihypertensives, lipid lowering agents and antithrombotics. Investigators were encouraged to follow guidelines in this area,” Robert Spanheimer, MD, medical director of diabetes at Takeda Pharmaceuticals, said at the annual meeting of the European Association for the Study of Diabetes.

Spanheimer said 47% of the PROactive cohort presented with a prior myocardial infarction and 19% presented with stroke. “A high number of patients presented with two or more entry criteria, so these are high-risk patients,” Spanheimer said.

PROactive enrolled 5,238 patients from 322 centers in 19 European countries. The mean age of the patient cohort was 62 years and about two-thirds were male. The mean BMI of patients in the study was 31 and their mean HbA1c was 7.8% to 7.9%.

Effects on cholesterol

During the study, which lasted 34.5 months, statin use increased between 12.3% and 12.5%. By the end of the study, 63.6% were on some sort of lipid lowering therapy.

Although both the pioglitazone and the placebo group experienced improvements in HDL cholesterol by six and 12 months, in the pioglitazone group HDL cholesterol increased 19% compared to 10% in the placebo group over baseline values.

In the pioglitazone group, triglycerides decreased 11.4%, whereas they increased 1.8% in the placebo group.

LDL cholesterol increased in both groups. The LDL-HDL ratio decreased by 9.5% in the pioglitazone group and decreased by 4.2% in the placebo group.

Concomitant therapies

When researchers conducted subgroup analyses between patients who were receiving any combination of insulin and patients who were not, they noted the effect was similar between the two groups.

Treatment with pioglitazone was associated with a 34-mg/dL reduction in triglycerides among patients receiving lipid-lowering drugs and a 34-mg/dL reduction among those not receiving lipid-lowering drugs. Placebo-treated patients saw a 9 mg/dL increase if they were receiving lipid-lowering drugs and no change if they were not.

Other lipid parameters were similarly unaffected by the presence of insulin treatment.

A further subgroup analysis focused on patients who were receiving metformin or sulfonylurea, or a combination of the two agents, along with pioglitazone. Improvements in lipid profiles were seen with pioglitazone whether the concomitant medications were present or not. – by Jeremy Moore

For more information:

Spanheimer R, Tan M, Yates J. The effects of long-term pioglitazone therapy on lipid profiles in high-risk type 2 diabetes patients: results from PROactive. Presented at: 42nd Annual Meeting of the European Association for the Study of Diabetes; Sept. 14-17, 2006. Copenhagen.