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Pioglitazone Superior to Sulfonylurea for Glycemic Control in Combo With Metform

A greater then a 1% drop in A1c was resulted from using piogliazone with metformin then glyburide with metformin. Pioglitazone (Actos; Takeda Pharmaceuticals North America, Inc.) is an effective and well-tolerated addition to metformin and offers glycemic control that is sustained for two years, a valuable long-term alternative to sulfonylureas.

The most widely used combination oral therapy for type 2 diabetes mellitus in clinical practice is currently metformin plus a sulfonylurea. Both of these agents have been shown to fail in monotherapy. The complementary mechanisms of action of pioglitazone, which can be used as monotherapy, metformin, and sulfonylureas suggest that combining them may provide long-term clinical benefits in diabetic patients.

In a randomized, double-blind, parallel group study, the researchers compared the efficacy, safety, and tolerability of the addition of pioglitazone vs gliclazide (GLIC) when combined with existing failing metformin (MET) therapy for type 2 diabetes.

The study population consisted of 630 patients, aged 35 to 75 years, with hemoglobin A1c (HbA1c) of 7.5 or higher and less than 11%, fasting C-peptide levels of 1.5 ng/mL (0.50 nmol/L) or higher, and stable or worsening glycemic control for three months or more prior to screening for study inclusion despite treatment with MET.

Patients were randomized to receive add-on therapy with pioglitazone, for 104 weeks. Measurements of HbA1c and fasting plasma glucose (FPG) were obtained at baseline and during the 104-week study.

The investigators found that at week 104, HbA1c reduction from baseline was 0.89% when pioglitazone was added to MET compared with 0.77% for GLIC added to MET, and the proportion of patients who achieved HbA1c less than 7.0% was 30.6% with pioglitazone compared with 25.2% for GLIC. In patients treated for a minimum of 18 months, the between-group difference for HbA1c reduction was statistically significant (P = .003).

Furthermore, a statistically significant between-group difference was observed in FPG reduction from baseline to week 104. Glycemic control achieved by the addition of pioglitazone to MET was sustained over two years, in contrast to the addition of GLIC, which showed signs of deterioration from approximately four months.

According to Sanjay Patel, MD, a family practitioner from Londonberry, New Hampshire, the weight increase using the combination of pioglitazone and MET has been his biggest concern with the therapy in practice. "We used to use metformin and a sulfonylurea, and have just recently switched to starting patients on metformin plus Actos and "one of the first things we noticed was fluid retention in elderly patients."

Because glycemic control with pioglitazone as add-on therapy to metformin was sustained over two years, the researchers concluded that the addition of pioglitazone to patients failing MET therapy might offer a distinct advantage over the addition of a sulfonylurea.

17th World Conference of Family Doctors: Abstract 3580. Presented Oct. 15, 2004.