European Medicines Agency Scientific Studies on Pioglitazone

The European Medicines Agency released a scientific study on the benefits and risks of the drug pioglitazone, also known as Actos, in January of 2007. This drug is currently used as a single treatment for Type 2 diabetes or in a dual combination form with metformin or sulphonylurea. When used alone, pioglitazone is typically used as therapy for the overweight patient whose Type 2 diabetes is not being controlled through diet and exercise and for whom the drug metformin is inappropriate. The combination drug is most often used in those patients who have insufficient glycemic control despite taking metformin alone or for those patients who have shown a level of intolerance to metformin. The results of the study showed that when pioglitazone was prescribed in conjunction with other anti-diabetic therapies such as insulin, the risk of macrovascular disease was greatly reduced. Macrovascular disease is common in those with long-term diabetes and refers to a disease of the large blood vessels in the body.

Clinical Support for Pioglitazone Application
Evidence was submitted which supported the application of pioglitazone, including four clinical trial reports which studied the safety of the drug when used in conjunction with insulin therapy. The studies were conducted according to prevailing ethical standards, and were random, double-blind, placebo controlled.

First Pioglitazone Study—PNFP-014
Pioglitazone was administered both in 15 mg dosages as well as 30 mg dosages in combination with insulin then compared with using insulin therapy alone. Participants in the studies were between the ages of 30 and 75, and had been on a fixed dose of insulin for at least a month prior to beginning the study. The mean baseline age was 57 years, with an average BMI of 33.6. Nearly 3/4ths of the participants in the study were Caucasian, with slightly more than half being female. Although the baseline systolic blood pressure was minimally higher in the group receiving pioglitazone plus insulin as opposed to the group receiving insulin alone, there were no other baseline variables involved. The patients who received both pioglitazone and insulin showed statistical decreases in the HbA1c levels which measure the average amount of sugar in the blood over a period of three months, and is different from glucose measurements. The HbA1c levels essentially give the physician an indication of how well the diabetes is being controlled.

Second Pioglitazone Study—PNFP-343
The second study compared doses of pioglitazone using 30 mg and 45 mg and was tested on subjects whose Type 2 diabetes was poorly controlled with insulin therapy alone. Participants were at least 18 years old, and had HbA1c values greater than 8%--any value over 6% indicates diabetes which is poorly controlled. The variables in this study were the HbA1c levels and the serum lipids which included total cholesterol, triglycerides, HDL, LDL and VLDL cholesterol and free fatty acids. The mean age was 56.5 and the mean BMI was 33.19, with 63% of the participants being Caucasian, and slightly more than half being male. The mean insulin dose was 69.2 units per day, and over one-fourth of the people in the study stated they also used other forms of anti-diabetic therapies in addition to insulin. The results of the study showed significant reduction in the use of insulin among the groups receiving both strengths of the drug, although there was a greater reduction in those using the 45 mg. tablets.

Third Pioglitazone Study—GLAT
The third study tested the safety and efficiency of the 30 mg. tablet of pioglitazone plus insulin as compared to insulin alone. The participants ranged in age from 30-70 years old who had HbA1c levels higher than 7.5% and were had taking insulin therapy for at least three months. The duration of this study was up to one year, and the variables included baseline HbA1c, Fasting serum levels, fasting serum lipids, FFA levels, urinary albumin/creatinine ratios, c-reactive protein levels, insulin dosage and rate of hypoglycemia. The mean age of the participants was 58.9 years, with a mean BMI of 32.1. The vast majority—96.4% were Caucasian, and the mean duration of the diabetes was 13.5 years. The HbA1c levels averaged 8.8%, which suggested the study population had very poorly controlled diabetes overall. After six months in the trial, those taking the pioglitazone had reduced their HbA1c levels by an average of .69%, while the placebo group had only reached an average of .14 %. The group taking pioglitazone was also able to reduce their insulin use by an average of 11.4 units per day. Read more ....