Efficacy, safety and tolerability of aleglitazar in patients with type 2 diabetes: pooled findings from three randomized phase III trials.
OBJECTIVE
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.
Center for Metabolic Research, VA San Diego Healthcare System, University of California, San Diego, CA, USA.
R R
RR
Henry
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
J B
JB
Buse
Roche (China) Holding Ltd, Beijing, China.
H
H
Wu
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
L
L
Durrwell
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
R
R
Mingrino
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
K
K
Jaekel
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
B
B
El Azzouzi
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
M
M
Andjelkovic
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
M
M
Herz
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010080:Oxazoles / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; D010080:Oxazoles; D013453:Sulfonylurea Compounds; D013876:Thiophenes; C517652:hemoglobin A1c protein, human; C542437:aleglitazar
PPAR-gamma agonist; glycaemic control; lipid-lowering therapy; metformin; sulphonylureas; type 2 diabetes