Experimental TZD Balaglitazone Shows Fewer Side Effects

Both agents stimulate PPAR (peroxisome proliferator-activated receptor)-gamma. Full PPAR-gamma agonists, like pioglitazone (Actos) and rosiglitazone (Avandia), are linked with bone loss, heart failure, edema and weight gain. But balaglitazone is a partial PPAR-gamma agonist. This study was the first to assess the safety of this type of agent.

According to Dr. Kim Henriksen, who led the research at Nordic Bioscience A/S, in Herlev, Denmark, "Adverse effects were less frequent with balaglitazone, especially at the level of edemas, weight gain and bone loss."

The research team randomized 409 patients with type 2 diabetes on stable insulin therapy to four groups that received balaglitazone 10 or 20mg, pioglitazone 45mg, or placebo once a day.

Compared to placebo, the treatment groups had significant drops in glycated hemoglobin (HbA1c) and fasting serum glucose levels. HbA1c fell by 0.099% with 10mg balaglitazone, 1.11% with 20mg, and 1.22% with pioglitazone. The pattern was similar for fasting serum glucose reductions.

Patients taking balaglitazone did not appear to lose bone mineral density, according to dual-energy X-ray absorptiometry analysis. The pioglitazone group, on the other hand, showed a trend toward a reduction, the researchers report.

Also, while balaglitazone at 10mg was associated with weight gain and fluid accumulation compared to the placebo, it was not as severe as in the 20mg and pioglitazone groups.

Before balaglitazone has a chance at regulatory approval, it still must undergo a phase III trial for cardiovascular safety.

Diabetes Metab Res Rev 2011;27:392-401.