Universität zu Köln

Erdmann, Erland ORCID: 0000-0002-9887-3736, Califf, Robert, Gerstein, Hertzel C., Malmberg, Klas, Ruilope, Luis, Schwartz, Gregory G., Wedel, Hans, Volz, Dietmar, Ditmarsch, Marc, Svensson, Anders and Bengus, Monica (2015). Effects of the dual peroxisome proliferator-activated receptor activator aleglitazar in patients with Type 2 Diabetes mellitus or prediabetes. Am. Heart J., 170 (1). S. 117 - 123. NEW YORK: MOSBY-ELSEVIER. ISSN 1097-5330

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Abstract

Background Insulin-resistant states, including type 2 diabetes (T2D) and prediabetes, are associated with elevated cardiovascular (CV) risk. Aleglitazar is a dual peroxisome proliferator-activated receptor alpha/gamma agonist with favorable insulinsensitizing and glucose-lowering actions, favorable effects on blood lipids, and an acceptable safety profile in short-time studies. Therefore, it was hypothesized that aleglitazar would reduce CV morbidity and mortality in patients with T2D mellitus and prediabetes (defined as glycosylated hemoglobin >= 5.7% to <6.5%) with previous CV complications. Study design ALEPREVENT was a phase III, multicenter, randomized, double-blind, trial comparing aleglitazar 150 mu g or placebo daily in patients with T2D or prediabetes with established, stable CV disease. The intended sample sizewas 19,000 with a primary efficacy measure of major adverse CV events. However, the trial was halted prematurely after 1,999 patients had been randomized because of futility and an unfavorable benefit risk ratio in another CV outcomes trial evaluating aleglitazar. Results At study termination after 58 +/- 38 days of treatment, data had been collected from 1,996 patients (1,581 with T2D and 415 with pre-T2D). Despite the brief duration of treatment, aleglitazar induced favorable changes in glycosylated hemoglobin and blood lipids, similar for participants with T2D or prediabetes. However, compared with placebo, aleglitazar increased the incidence of hypoglycemia (86 vs 166; P < .0001), and muscular events (3 vs 12; P = .012). Conclusions Even within a short duration of exposure, aleglitazar was associated with excess adverse events, corroborating the findings of a larger and longer trial in T2D. Coupled with the previous failure of several other peroxisome proliferator-activated receptor alpha/gamma activators, this class now holds little promise for CV therapeutics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Erdmann, Erland UNSPECIFIED orcid.org/0000-0002-9887-3736 UNSPECIFIED Califf, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerstein, Hertzel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Malmberg, Klas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruilope, Luis UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwartz, Gregory G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wedel, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Volz, Dietmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Ditmarsch, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Svensson, Anders UNSPECIFIED UNSPECIFIED UNSPECIFIED Bengus, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-399913
DOI:	10.1016/j.ahj.2015.03.021
Journal or Publication Title:	Am. Heart J.
Volume:	170
Number:	1
Page Range:	S. 117 - 123
Date:	2015
Publisher:	MOSBY-ELSEVIER
Place of Publication:	NEW YORK
ISSN:	1097-5330
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE CORONARY SYNDROME; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; RISK; EVENTS Multiple languages Cardiac & Cardiovascular Systems Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39991