Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 23;8(1):e12268.
doi: 10.1002/trc2.12268. eCollection 2022.

Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers

Caroline Holm Nørgaard  1   2 , Sarah Friedrich  3 , Charlotte Thim Hansen  4 , Thomas Gerds  5 , Clive Ballard  6 , Daniel Vega Møller  4 , Lotte Bjerre Knudsen  7 , Kajsa Kvist  4 , Bernard Zinman  8 , Ellen Holm  9 , Christian Torp-Pedersen  1   10 , Lina Steinrud Mørch  4
Affiliations

Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers

Caroline Holm Nørgaard et al. Alzheimers Dement (N Y). .

Abstract

Introduction: People with type 2 diabetes have increased risk of dementia. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are among the promising therapies for repurposing as a treatment for Alzheimer's disease; a key unanswered question is whether they reduce dementia incidence in people with type 2 diabetes.

Methods: We assessed exposure to GLP-1 RAs in patients with type 2 diabetes and subsequent diagnosis of dementia in two large data sources with long-term follow-up: pooled data from three randomized double-blind placebo-controlled cardiovascular outcome trials (15,820 patients) and a nationwide Danish registry-based cohort (120,054 patients).

Results: Dementia rate was lower both in patients randomized to GLP-1 RAs versus placebo (hazard ratio [HR]: 0.47 (95% confidence interval [CI]: 0.25-0.86) and in the nationwide cohort (HR: 0.89; 95% CI: 0.86-0.93 with yearly increased exposure to GLP-1 RAs).

Discussion: Treatment with GLP-1 RAs may provide a new opportunity to reduce the incidence of dementia in patients with type 2 diabetes.

Keywords: dementia; glucagon‐like peptide‐1 receptor agonists; randomized controlled trial; real‐world evidence; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

CHN, TG, EH, and CTP report no conflicts of interests. SF reports grants from Novo Nordisk related to the manufacture of GLP‐1 RAs during the conduct of the study and support for attending meetings and/or travel from the German Research Foundation (payments made to institution); she has also been secretary of the German Consortium in Statistics (DAGStat). CTMH, DVM, KK are Novo Nordisk employees and report personal fees from Novo Nordisk A/S related to the manufacture of GLP‐1 RAs (salary and shareholder), during the conduct of the study. KK also reports Novo Nordisk stock in pension funds. CTMH is also inventor on a patent application related to GLP‐1 compounds and indications (patent is owned by Novo Nordisk and she receives no financial or other benefits from it) and is a minor stockholder of Novo Nordisk A/S. CB reports grants and personal fees from Acadia, Addex, Exciva, Janssen, Suven, and Lundbeck; personal fees from Roche, Otsuka, Biogen, Eli Lilly, Sunovion, Novo Nordisk, and AARP; grants and personal fees from Synexus, outside the submitted work; he also reports the following grants to his institution (UoE) from: 2021 ADDF, 2020 UKRI, 2019 IMI2, NIH, Charles Wolfson Foundation, Novo Nordisk, 2018 MRC, Synexus, Capital, award from Dennis and Mireille Gillings Foundation, Novartis, and Oryzon; honoraria from Harvard University (to institution, UoE), GE Healthcare, Acadia, AARP, and Addex. LBK is a Novo Nordisk employee and an inventor on numerous patents and applications related to GLP‐1 compounds and indications; all patents are owned by Novo Nordisk, which markets liraglutide and semaglutide, and she receives no financial or other benefits from them. BZ reports grants and personal fees from Novo Nordisk during the conduct of the study, and personal fees from Eli Lilly, Merck, Boehringer Ingelheim, and Janssen, outside the submitted work. LSM is a Novo Nordisk employee and reports personal fees from Novo Nordisk A/S related to the manufacture of GLP‐1 RA (salary) during the conduct of the study; she is also vice chair of the Danish Society for Pharmacoepidemiology and is on the executive committee for the Nordic PharmacoEpidemiological Network.

Figures

FIGURE 1
FIGURE 1
Time to dementia with GLP‐1 RAs versus placebo in pooled RCTs. In the pooled RCTs, 15 patients randomized to a GLP‐1 RA and 32 patients randomized to placebo developed dementia. GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; RCT, randomized controlled trial
FIGURE 2
FIGURE 2
HRs for dementia with yearly increase in exposure duration to GLP‐1 RAs and other second‐line diabetes treatments in the nationwide cohort. Cox proportional hazards regression models conducted for exposure to each treatment. Estimates denote the HR for yearly increase in duration of exposure. The models were adjusted for history of stroke, myocardial infarction, hypertension, educational attainment, and diabetes duration. Sex, age, and calendar date were included via matching. SGLT‐2 inhibitors (HR: 0.81; 95% CI: 0.68–0·97) were not available throughout the entire study period. CI, confidence interval; DPP‐4, dipeptidyl peptidase‐4; GLP‐1, glucagon‐like peptide‐1; HR, hazard ratio; SGLT‐2, sodium‐glucose co‐transporter‐2
FIGURE 3
FIGURE 3
HRs for dementia with yearly increase in exposure duration to GLP‐1 RAs according to subgroup in the nationwide cohort. Cox proportional hazards regression models conducted for exposure to GLP‐1 in various subgroups. Estimates denote the HR for yearly increase in duration of exposure. The models were adjusted for history of stroke, myocardial infarction, hypertension, educational attainment, and diabetes duration. Sex, age, and calendar date were included via matching. CI, confidence interval; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; HR, hazard ratio
See this image and copyright information in PMC

References

    1. Prince M, Karagiannidou M, Comas‐Herrera A, Knapp M. World Alzheimer Report 2016. Improving healthcare for people living with dementia. Alzheimers Dis Int. 2016:1‐127. https://www.alzint.org/u/WorldAlzheimerReport2016.pdf.
    1. International Diabetes Federation. IDF Diabetes Atlas Ninth Edition 2019. 2019; - PubMed
    1. Rawlings AM, Sharrett AR, Schneider AL, et al. Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med. 2014;161(11):785‐793. 10.7326/m14-0737. - DOI - PMC - PubMed
    1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet (London, England). 2020;396(10248):413‐446. 10.1016/s0140-6736(20)30367-6. - DOI - PMC - PubMed
    1. Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and risk of dementia: a meta‐analysis of prospective observational studies. J Diabetes Invest. 2013;4(6):640‐650. 10.1111/jdi.12087. - DOI - PMC - PubMed

LinkOut - more resources