title: Aleglitazar, a dual peroxisome proliferator-activated receptor-α/γ agonist, improves insulin sensitivity, glucose control and lipid levels in people with type 2 diabetes: findings from a randomized, double-blind trial.
abstract: The present single-centre, randomized, double-blind, placebo-controlled phase II study investigated the effect of the balanced dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on whole-body and liver insulin sensitivity, β-cell function and other components of cardiometabolic syndrome after 16 weeks of treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy who received once-daily 150 µg aleglitazar or matching placebo as add-on therapy to metformin. Baseline and 16-week assessments included a two-step hyperinsulinaemic-euglycaemic clamp, followed by a hyperglycaemic clamp, as well as evaluation of glycated haemoglobin (HbA1c), lipids and safety variables. The primary endpoint was change in whole-body insulin sensitivity (M-value) from baseline compared with placebo, derived from the second clamp step. M-value improved significantly from baseline with aleglitazar (n = 16) compared with placebo (n = 24; p = 0.05 for difference between arms). We found statistically significant treatment differences with aleglitazar versus placebo in fasting hepatic insulin resistance index (p = 0.01), and in total glucose disposal (p = 0.03) at the second insulin infusion step. Aleglitazar treatment resulted in significant improvements in HbA1c and lipids and was well tolerated.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: A O
authors.initials: AO
authors.lastname: Stirban
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Andjelkovic
authors.affiliation: Profil, Neuss, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.affiliation: Profil, Neuss, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Nosek
authors.affiliation: Profil, Neuss, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Institute of Clinical Physiology, Pisa, Italy.
authors.forename: A
authors.identifier: 0000-0003-2594-1651
authors.initials: A
authors.lastname: Gastaldelli
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Herz
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D024821:Metabolic Syndrome / Q000517:prevention & control; D008875:Middle Aged; D010080:Oxazoles / Q000008:administration & dosage*; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D013876:Thiophenes; C542437:aleglitazar
keywords: aleglitazar; dual peroxisome proliferator-activated receptor agonist; glucose; insulin sensitivity; lipids; type 2 diabetes