Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial


Tali Cukierman-Yaffe 1, Hertzel C Gerstein 2, Helen M Colhoun 3, Rafael Diaz 4, Luis-Emilio García-Pérez 5, Mark Lakshmanan 5, Angelyn Bethel 5, Denis Xavier 6, Jeffrey Probstfield 7, Matthew C Riddle 8, Lars Rydén 9, Charles Messan Atisso 5, Stephanie Hall 10, Purnima Rao-Melacini 10, Jan Basile 11, William C Cushman 12, Edward Franek 13, Matyas Keltai 14, Fernando Lanas 15, Lawrence A Leiter 16, Patricio Lopez-Jaramillo 17, Valdis Pirags 18, Nana Pogosova 19, Peter J Raubenheimer 20, Jonathan E Shaw 21, Wayne H-H Sheu 22, Theodora Temelkova-Kurktschiev 23

Main idea: Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated.


Background: Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial.

Methods: REWIND is a randomized, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors. Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1·5 mg) or an equal volume of matching placebo. We followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide or placebo. After post-hoc adjustment for individual standardized baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those who were given the drug. The cognitive outcome occurred in 405 per 100 patient-years in participants assigned dulagsutide and 4·35 in people assigned placebo.


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