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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
Author(s) -
Stirban A. O.,
Andjelkovic M.,
Heise T.,
Nosek L.,
Fischer A.,
Gastaldelli A.,
Herz M.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12620
Subject(s) - metformin , placebo , medicine , insulin resistance , endocrinology , type 2 diabetes , insulin , diabetes mellitus , agonist , glucose clamp technique , clinical endpoint , randomized controlled trial , receptor , insulin sensitivity , alternative medicine , pathology
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.