Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 10, 2015; 6(9): 1092-1096
Published online Aug 10, 2015. doi: 10.4239/wjd.v6.i9.1092
Interpretation of cardiovascular outcome trials in type 2 diabetes needs a multiaxial approach
Odd Erik Johansen
Odd Erik Johansen, Boehringer Ingelheim Norway KS, 1373 Asker, Norway
Odd Erik Johansen, Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, 1309 Rud, Norway
Author contributions: Johansen OE prepared and wrote this editorial.
Conflict-of-interest statement: I am employed by Boehringer Ingelheim Norway KS.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Odd Erik Johansen, MD, PhD, Medical Director, Boehringer Ingelheim Norway KS, P.O. Box 405, 1373 Asker, Norway. odd_erik.johansen@boehringer-ingelheim.com
Telephone: +47-91817674 Fax: +47-66761330
Received: January 20, 2015
Peer-review started: January 22, 2015
First decision: March 6, 2015
Revised: June 25, 2015
Accepted: July 21, 2015
Article in press: July 23, 2015
Published online: August 10, 2015
Processing time: 205 Days and 22.7 Hours
Abstract

In cardiovascular (CV) diabetology a “one-size fits-all” approach needs caution as vasculopathy and CV manifestations in patients with type 2 diabetes (T2D) with short disease duration are different as compared to those with longer duration. This is of relevance when interpreting results of CV outcome trials as responses to any intervention aimed to reduce CV risk might be different in patients with established vasculopathy as compared to those without, where also the duration of the intervention may play a role. Additionally, the mode-of-action of the intervention and its assumed time to peak CV risk modulation need to be taken into account: an intervention with possibly immediate effects, like on blood pressure or other direct functional dynamic parameters such as endothelial function or renal hemodynamics, could likely provide a meaningful impact on CV outcomes over a shorter time span than interventions that primarily target pathways that work on atherosclerotic processes, organ-remodelling, or vessel integrity. We are now faced with CV outcome results to interpret from a plethora of outcomes trials in T2D, some of which are testing the CV risk modulation predominantly beyond glucose lowering, e.g., as is the case for several trials testing the newer therapy classes di-peptidyl peptidase-4 inhibitors, glucagon-like protein-1 receptor analogues and sodium glucose co-transporter-2 inhibitors, and this paper reviews the data that support a call for a multiaxial approach to interpret these results.

Keywords: Type 2 diabetes; Pharmaceutical; Risk reduction; Outcomes; Cardiovascular

Core tip: Vasculopathy and cardiovascular (CV) manifestations in patients with type 2 diabetes differ dependent on disease duration. This literature review supports that it is necessary to contextualize results of CV outcome trials in diabetes to diabetes duration as well as duration and mode of action of the intervention, which may be of particular relevance for those interventions that primarily target pathways related to atherosclerotic processes, organ-remodelling, or vessel integrity. Several CV outcome trials testing newer therapy classes (i.e., di-peptidyl peptidase-4 inhibitors, glucagon-like protein-1 receptor analogues and sodium glucose co-transporter-2 inhibitors) are now due to report and a multiaxial approach to interpret these results is needed.