oxyntomodulin and Cognitive-Dysfunction

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.

Topics: Adult; Aged; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Male; Middle Aged; Recombinant Fusion Proteins; Treatment Outcome

Topics: Animals; Apoptosis; Cell Line; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Epilepsy; Glucagon-Like Peptides; Hippocampus; Inflammasomes; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Pentylenetetrazole; Seizures

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cognition; Cognitive Dysfunction; Gene Expression Regulation; Glucagon-Like Peptides; Hippocampus; Histone-Lysine N-Methyltransferase; Histones; Inflammation; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Quinazolines