Efficacy, safety and tolerability of aleglitazar in patients with type 2 diabetes: pooled findings from three randomized phase III trials

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2015-06, Vol.17 (6), p.560-565
• Main Authors: Henry, R. R., Buse, J. B., Wu, H., Durrwell, L., Mingrino, R., Jaekel, K., El Azzouzi, B., Andjelkovic, M., Herz, M.
• Format: Article
• Language: English
• Subjects: Antidiabetics; Blood Glucose - analysis; Body weight; Clinical trials; Congestive heart failure; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Therapy, Combination; Edema; Evidence-based medicine; Fasting - blood; Female; glycaemic control; Glycated Hemoglobin A - analysis; Hemoglobin; Humans; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemic Agents - therapeutic use; Insulin; Insulin resistance; Insulin Resistance - physiology; lipid-lowering therapy; Lipids; Lipids - blood; Male; Metformin; Metformin - therapeutic use; Middle Aged; Oxazoles - therapeutic use; Patients; PPAR-gamma agonist; Sulfonylurea Compounds - therapeutic use; sulphonylureas; Thiophenes - therapeutic use; type 2 diabetes
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12455

Aims To evaluate the potential efficacy, safety and tolerability of aleglitazar as monotherapy or add‐on therapy to metformin or to a sulphonylurea (either alone or in combination with metformin). Methods We conducted a pooled analysis of data from three randomized phase III clinical trials of aleglitazar in patients with type 2 diabetes (n = 591). The three studies focused on: (i) aleglitazar alone; (ii) aleglitazar and metformin; and (iii) aleglitazar and sulphonylurea with or without metformin. Patients were randomized to 26 weeks' treatment with aleglitazar 150 µg/day or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) concentration from baseline to week 26. Secondary endpoints included changes in lipids, fasting plasma glucose and homeostatic model assessment of insulin resistance (HOMA‐IR) at week 26. Results Reductions in HbA1c concentration from baseline to week 26 were statistically significantly greater with aleglitazar than with placebo. Aleglitazar treatment was associated with more beneficial changes in lipid profiles and HOMA‐IR values than was placebo. Aleglitazar was generally well tolerated, with no reports of congestive heart failure. The incidence of peripheral oedema was similar in both groups. Change in body weight was +1.37 kg with aleglitazar and −0.53 kg with placebo. Hypoglycaemia was more frequently reported with aleglitazar (7.8%) than with placebo (1.7%), a result probably driven by the type of background medication. Conclusions Development of aleglitazar was halted because of a lack of cardiovascular efficacy and peroxisome proliferator‐activated receptor‐related side effects in patients with type 2 diabetes post‐acute coronary syndrome; however, in the present studies, aleglitazar was well tolerated and effective in improving HbA1c, insulin resistance and lipid variables.