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


Journal

The Lancet. Neurology
ISSN: 1474-4465
Titre abrégé: Lancet Neurol
Pays: England
ID NLM: 101139309

Informations de publication

Date de publication:
07 2020
Historique:
received: 13 02 2020
revised: 10 04 2020
accepted: 23 04 2020
entrez: 21 6 2020
pubmed: 21 6 2020
medline: 15 9 2020
Statut: ppublish

Résumé

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. REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1-5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85-1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79-0·95; p=0·0018). 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. Eli Lilly and Company.

Sections du résumé

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 randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m
FINDINGS
Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1-5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85-1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79-0·95; p=0·0018).
INTERPRETATION
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.
FUNDING
Eli Lilly and Company.

Identifiants

pubmed: 32562683
pii: S1474-4422(20)30173-3
doi: 10.1016/S1474-4422(20)30173-3
pii:
doi:

Substances chimiques

Hypoglycemic Agents 0
Immunoglobulin Fc Fragments 0
Recombinant Fusion Proteins 0
Glucagon-Like Peptides 62340-29-8
dulaglutide WTT295HSY5

Banques de données

ClinicalTrials.gov
['NCT01394952']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

582-590

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Tali Cukierman-Yaffe (T)

Endocrinology Institute, Gertner Institute, Sheba Medical Center, Ramat-Gan, Israel; Epidemiology Department, Sackler School of Medicine, Herceg Institute of Aging, Tel Aviv University, Tel Aviv, Israel.

Hertzel C Gerstein (HC)

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. Electronic address: gerstein@mcmaster.ca.

Helen M Colhoun (HM)

University of Edinburgh, Edinburgh, UK.

Rafael Diaz (R)

Estudios Clínicos Latino América, Rosario, Argentina.

Luis-Emilio García-Pérez (LE)

Eli Lilly and Company, Indianapolis, IN, USA.

Mark Lakshmanan (M)

Eli Lilly and Company, Indianapolis, IN, USA.

Angelyn Bethel (A)

Eli Lilly and Company, Indianapolis, IN, USA.

Denis Xavier (D)

St John's Medical College, Bangalore, India.

Jeffrey Probstfield (J)

Department of Medicine, University of Washington, Seattle, WA, USA.

Matthew C Riddle (MC)

Department of Medicine, Oregon Health and Science University Portland, OR, USA.

Lars Rydén (L)

Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden.

Charles Messan Atisso (CM)

Eli Lilly and Company, Indianapolis, IN, USA.

Stephanie Hall (S)

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Purnima Rao-Melacini (P)

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Jan Basile (J)

Medical University of South Carolina, Charleston, SC, USA.

William C Cushman (WC)

Memphis Veterans Affairs Medical Center, Memphis, TN, USA.

Edward Franek (E)

Mossakowski Medical Research Centre, Polish Academy of Sciences and Central Clinical Hospital, Warsaw, Poland.

Matyas Keltai (M)

Semmelweis University, Hungarian Institute of Cardiology, Budapest, Hungary.

Fernando Lanas (F)

Universidad de La Frontera, Temuco, Chile.

Lawrence A Leiter (LA)

Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Patricio Lopez-Jaramillo (P)

Masira Research Institute, Medical School, Universidad de Santander, Bucaramanga, Colombia.

Valdis Pirags (V)

Latvijas Universitate, Riga, Latvia.

Nana Pogosova (N)

National Medical Research Center of Cardiology, Moscow, Russia.

Peter J Raubenheimer (PJ)

Department of Medicine, University of Cape Town, Cape Town, South Africa.

Jonathan E Shaw (JE)

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Wayne H-H Sheu (WH)

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Theodora Temelkova-Kurktschiev (T)

Robert Koch Medical Center, Sofia, Bulgaria.

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Classifications MeSH