EASD 2020 Highlights

Conference summaries


Exploring potential mediators of the cardiovascular benefit of dulaglutide in REWIND

Presented by:

Hertzel C. Gerstein, MD

  • Only 36% of the impact of dulaglutide on MACE can be accounted for by its effects on HbA1c.
  • The effects of dulaglutide on weight and systolic BP have little or no statistical contribution to its benefits on MACE.
  • The mechanism(s) responsible for the impact of dulaglutide on MACE still remain(s) to be defined.

What do we already know about this topic?

  • The REWIND cardiovascular (CV) outcomes trial assessed the effect of dulaglutide on first major adverse cardiac event (MACE) in 9901 people with type 2 diabetes and either CV risk factors or CV disease.1
  • Dulaglutide significantly reduced MACE in the presence or absence of prior CV disease.1
  • Dulaglutide also reduced HbA1c, weight and systolic blood pressure (BP).1

How was this study conducted?

  • This study assessed whether the effects of dulaglutide on HbA1c, weight and systolic BP can account for its effect on MACE.
  • Updated mean HbA1c, weight and systolic BP were estimated as the mean of consecutive measures before the MACE outcome or study end (or censorship if no MACE outcome).
  • The relationship of each variable’s updated mean value and MACE was estimated.
  • If the relationship was significant, the effect of dulaglutide on MACE was re-estimated in a new Cox model that included dulaglutide allocation, baseline value of the variable and updated mean of the variable as time dependent covariates.

What does this study add?

  • Up to 36% of the CV benefit of dulaglutide on MACE can be statistically accounted for by its effect on HbA1c.
  • The effects of dulaglutide on weight and systolic BP did not statistically account for the effects on MACE (Fig. 1).


How does this study impact clinical practice?

  • Most of the impact of dulaglutide on MACE cannot be accounted for by its effects on HbA1c, weight or systolic BP.
  • The mechanism behind the impact of MACE remains unclear, but might include direct effects on small or large vessels, anti-inflammatory effects, or other processes.



  1. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-30.


Related content


This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:

Hertzel C. Gerstein, MD
Master University and Hamilton Health Sciences, Hamilton, Ontario, Canada

The presenting authors of the original session had no part in the creation of this conference highlights summary. 

The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.


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