A study, named COMPLEMENT, found tha patients with type 2 diabetes on statin therapy for diabetic dyslipidemia who were switched to the oral anti-diabetic drug Actos ( Pioglitazone ) from Rosiglitazone ( Avandia ) showed significant improvements, beyond those resulting from traditional cholesterol-lowering statin therapy, in key lipid parameters.

These effects were independent of blood glucose control, which remained stable after the therapies were changed.

Diabetic dyslipidemia, a risk factor for cardiovascular disease, is a profile of lipid abnormalities typically seen in people with type 2 diabetes.
The pattern consists of elevated triglycerides, reduced levels of HDL cholesterol, normal or slightly-elevated levels of total and LDL cholesterol, and a shift toward smaller and denser LDL cholesterol particles.
While dyslipidemia also occurs in people who do not have diabetes, the specific abnormalities in the lipoprotein pattern characteristic of diabetic dyslipidemia appear to add excess risk for people with diabetes.

"What is unique about diabetic dyslipidemia is that lipid profiles may show normal levels of LDL, yet lower HDL and increased triglycerides that single lipid therapy alone may not address," noted Spanheimer.

Previously reported results from a head-to-head, randomized, controlled study showed that Pioglitazone significantly improved lipid levels to a greater extent than Rosiglitazone.

COMPLEMENT was designed to determine whether these effects would remain if patients were on a statin " currently a recommended therapy for people with diabetic dyslipidemia" in addition to Pioglitazone or Rosiglitazone.

Pioglitazone and Rosiglitazone are members of a class of drugs called thiazolidinediones ( TZDs ) that reduce blood glucose levels by targeting insulin resistance, a core metabolic dysfunction of type 2 diabetes.

The multicenter, single-arm, 17-week, open-label study enrolled 305 people with type 2 diabetes taking statins ( with or without other lipid-lowering drugs ) along with Rosiglitazone alone or in combination with another oral anti-diabetic drug.

Patients were then switched to Pioglitazone ( 30 mg QD, titrated to 45 mg QD at investigator discretion ), while maintaining their statin with or without other lipid-lowering therapy.

Blood glucose and lipid levels ( including fasting triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol ) were measured at the start of the study when patients were on Rosiglitazone, and during the time the patients were on Pioglitazone.

The results showed Pioglitazone significantly lowered lipid levels when patients were switched from Rosiglitazone.

Additionally, the effects were seen regardless of age or gender, or if patients took Fenofibrate in addition to statin therapy. These improvements were consistent with those observed in the previous head-to-head study.
Specifically:

- Triglycerides were reduced by nearly 21 percent ( P<0.0001 ), total cholesterol was reduced by 10.5 percent ( P<0.0001 ),
- LDL-C decreased by 1.1 percent ( P=0.040 ),
- HDL-C: mean HDL particle concentration increased 3.8 micromol/L, and mean levels of Apo A1 increased by 9.7 mg/dL.
- LDL/VLDL: mean LDL particle size increased 0.23 nm and mean LDL particle concentration decreased 189 nmol/L, indicating there were fewer LDL particles and they were larger and more buoyant without an increase in LDL. Mean VLDL particle concentration decreased 44.9 nmol/L. Additionally, mean levels of Apo B decreased by 2.6 mg/dL.

Pioglitazone works by directly targeting insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels.
Pioglitazone is taken once daily as an adjunct to diet and exercise, and is approved for use for type 2 diabetes as monotherapy to lower blood glucose and in combination therapy with Insulin, sulfonylureas or Metformin.

Pioglitazone can cause fluid retention that may lead to or worsen heart failure.
The patients can experience rapid weight gain, fluid retention, or shortness of breath while taking Pioglitazone.
Pioglitazone is not recommended in moderate to severe heart failure.
Physicians should perform a blood test to check for liver problems before starting Pioglitazone and periodically thereafter.
Patients should not take Pioglitazone if they have active liver disease.
Pioglitazone could increase the chance of becoming pregnant.
Some people taking Pioglitazone may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia.
When taking Pioglitazone with Insulin or sulfonylureas, the patient may be at risk for low blood glucose.

Source: American Diabetes Association ( ADA ) 65th Annual Scientific Sessions, 2005


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