Efficacy and safety of the partial PPARγ agonist balaglitazone compared with pioglitazone and placebo: A phase III, randomised, parallel-group study in patients with type 2 diabetes on stable insulin therapy

Treatment of patients with full PPARγ agonists is associated with weight gain, heart failure, peripheral oedema and bone loss. However, the safety of partial PPARγ agonists has not been established in a clinical trial. The BALLET trial aimed to establish the glucose-lowering effects and safety parameters of the partial PPARγ agonist balaglitazone in diabetic patients on stable insulin therapy. 409 subjects from 3 countries with type 2 diabetes on stable insulin therapy were randomised to 26 weeks of double-blind treatment with once daily doses of 10 or 20mg balaglitazone, 45 mg pioglitazone, or matching placebo (n≥99 in each group). The primary endpoint was the efficacy of balaglitazone 10mg and 20mg versus placebo on the absolute change in HbA(1c) . Secondary endpoints included levels of fasting serum glucose (FSG), and changes in body composition and bone mineral density as measured by DXA, with comparison to pioglitazone 45mg. Clinicaltrials.gov identifier: NCT00515632. In the 10 and 20mg balaglitazone groups, and in the pioglitazone 45mg group, significant reductions in HbA(1c) levels were observed (-0.99%, -1.11% and -1.22% respectively (p <0.0001)) versus placebo. FSG was similarly reduced in all treatment arms. DXA analyses showed balaglitazone 10mg led to less fat and fluid accumulation and no change in bone mineral density, when compared to pioglitazone. In the balaglitazone 10mg treated group clinically relevant reductions in HbA(1c) and glucose levels were observed, although it appeared to be a little less potent that pioglitazone 45mg. On the other hand significantly less fluid and fat accumulation were observed, highlighting this treatment regimen for further studies.