TY - JOUR
T1 - Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo
T2 - a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy
AU - Henriksen, Kim
AU - Byrjalsen, Inger
AU - Qvist, Per
AU - Beck-Nielsen, Henning
AU - Hansen, Gitte
AU - Riis, Bente J
AU - Perrild, Hans
AU - Svendsen, Ole Lander
AU - Gram, Jeppe
AU - Karsdal, Morten A
AU - Christiansen, Claus
AU - BALLET Trial Investigators
N1 - Copyright © 2011 John Wiley & Sons, Ltd.
PY - 2011/5
Y1 - 2011/5
N2 - Background: Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. Methods: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A1c. Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. Results: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A1c levels were observed (-0.99, - 1.11, and - 1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. Conclusion: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA1c. With the 10 mg dose, the benefits (glucose & HgA1c lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.
AB - Background: Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. Methods: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A1c. Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. Results: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A1c levels were observed (-0.99, - 1.11, and - 1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. Conclusion: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA1c. With the 10 mg dose, the benefits (glucose & HgA1c lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.
U2 - 10.1002/dmrr.1187
DO - 10.1002/dmrr.1187
M3 - Journal article
SN - 1520-7552
VL - 27
SP - 392
EP - 401
JO - Diabetes - Metabolism: Research and Reviews (Print Edition)
JF - Diabetes - Metabolism: Research and Reviews (Print Edition)
IS - 4
ER -
