Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

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Abstract

Introduction

The prevalence of major and mild cognitive impairment (CI) in type-2 diabetes older patients is 15–25% and 30–60%, respectively, thus affecting quality of life and health outcomes. There is, therefore, the need of head-to-head studies aiming at identifying the optimal treatment for individuals with type-2 diabetes at increased risk of mild and major CI. This study focuses on the risk of developing mild and major CI in Danish patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 analogues (GLP-1a) using administrative and healthcare registers.

Methods

An active comparator design with a 3-year follow-up period was used. The main outcome was the hospital admission with a diagnosis of mild CI or major CI. Multivariate Cox Regression analysis was performed using the high-dimensional propensity score to obtain adjusted Hazard Ratio (HR) estimates. Inverse probability of treatment weighting (IPTW) and marginal structured model were used to calculate risk differences while accounting for the variations of confounders throughout the follow-up period.

Results

Our results show a significant higher risk of major CI between DPP-4i and GLP-1a in unadjusted [HR (95% CI) = 3.13 (2.45–4.00), p < 0.001] and adjusted analyses [HR (95% CI) = 1.58 (1.22–2.06), p = 0.001]. No statistically significant differences were observed for mild CI. IPTW resulted stable throughout the follow-up period. Marginal structure modeling (β (95% CI) = 0.022 (0.020–0.024), p < 0.001) resulted in a higher risk of major CI for DPP-4i when compared to GLP-1a.

Discussion

DPP-4i was associated with an increased risk of developing major CI when compared to GLP-1a among older individuals with type-2 diabetes.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00415-024-12300-9.

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Most cited references 37

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The Danish National Patient Registry: a review of content, data quality, and research potential

Morten Schmidt, Sigrun Alba Johannesdottir Schmidt, Jakob Sandegaard … (2015)

Background The Danish National Patient Registry (DNPR) is one of the world’s oldest nationwide hospital registries and is used extensively for research. Many studies have validated algorithms for identifying health events in the DNPR, but the reports are fragmented and no overview exists. Objectives To review the content, data quality, and research potential of the DNPR. Methods We examined the setting, history, aims, content, and classification systems of the DNPR. We searched PubMed and the Danish Medical Journal to create a bibliography of validation studies. We included also studies that were referenced in retrieved papers or known to us beforehand. Methodological considerations related to DNPR data were reviewed. Results During 1977–2012, the DNPR registered 8,085,603 persons, accounting for 7,268,857 inpatient, 5,953,405 outpatient, and 5,097,300 emergency department contacts. The DNPR provides nationwide longitudinal registration of detailed administrative and clinical data. It has recorded information on all patients discharged from Danish nonpsychiatric hospitals since 1977 and on psychiatric inpatients and emergency department and outpatient specialty clinic contacts since 1995. For each patient contact, one primary and optional secondary diagnoses are recorded according to the International Classification of Diseases. The DNPR provides a data source to identify diseases, examinations, certain in-hospital medical treatments, and surgical procedures. Long-term temporal trends in hospitalization and treatment rates can be studied. The positive predictive values of diseases and treatments vary widely (<15%–100%). The DNPR data are linkable at the patient level with data from other Danish administrative registries, clinical registries, randomized controlled trials, population surveys, and epidemiologic field studies – enabling researchers to reconstruct individual life and health trajectories for an entire population. Conclusion The DNPR is a valuable tool for epidemiological research. However, both its strengths and limitations must be considered when interpreting research results, and continuous validation of its clinical data is essential.

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The Danish Civil Registration System.

Carsten Bøcker Pedersen (2011)

The Danish Civil Registration System (CRS) was established in 1968, and all persons alive and living in Denmark were registered for administrative use. CRS includes individual information on the unique personal identification number, name, gender, date of birth, place of birth, citizenship, identity of parents and continuously updated information on vital status, place of residence and spouses. Since 1968, CRS has recorded current and historical information on all persons living in Denmark. Among persons born in Denmark in 1960 or later it contains complete information on maternal identity. For women born in Denmark in April 1935 or later it contains complete information on all their children. CRS contains complete information on immigrations and emigrations from 1969 onwards, permanent residence in a Danish municipality from 1971 onwards, and full address in Denmark from 1977 onwards. CRS in connection with other registers and biobanks will continue to provide the basis for significant knowledge relevant to the aetiological understanding and possible prevention of human diseases.

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The Danish National Prescription Registry.

Helle Wallach Kildemoes, Henrik Toft Sørensen, Jesper Hallas (2011)

Individual-level data on all prescription drugs sold in Danish community pharmacies has since 1994 been recorded in the Register of Medicinal Products Statistics of the Danish Medicines Agency. The register subset, termed the Danish National Prescription Registry (DNPR), contains information on dispensed prescriptions, including variables at the level of the drug user, the prescriber, and the pharmacy. Reimbursement-driven record keeping, with automated bar-code-based data entry provides data of high quality, including detailed information on the dispensed drug. The possibility of linkage with many other nationwide individual-level data sources renders the DNPR a very powerful pharmacoepidemiological tool.

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Author and article information

Contributors

Maurizio Sessa:

ORCID: http://orcid.org/0000-0003-0874-4744

maurizio.sessa@sund.ku.dk

Journal

Journal ID (nlm-ta): J Neurol

Journal ID (iso-abbrev): J Neurol

Title: Journal of Neurology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5354

ISSN (Electronic): 1432-1459

Publication date (Electronic): 22 March 2024

Publication date PMC-release: 22 March 2024

Publication date (Print): 2024

Volume: 271

Issue: 6

Pages: 3417-3425

Affiliations

[1 ]Department of Drug Design and Pharmacology, University of Copenhagen, ( https://ror.org/035b05819) Jagtvej 160, 2100 Copenhagen, Denmark

[2 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Pharmacovigilance and Clinical Research, International Centre for Pesticides and Health Risk Prevention, Department of Biomedical and Clinical Sciences (DIBIC), ASST Fatebenefratelli-Sacco University Hospital, , Università Degli Studi Di Milano, ; Milan, Italy

[3 ]Department of Clinical and Experimental Medicine, University of Messina, ( https://ror.org/05ctdxz19) 98125 Messina, Italy

[4 ]GRID grid.420417.4, ISNI 0000 0004 1757 9792, Scientific Institute, , IRCCS E. Medea, ; Bosisio Parini, LC Italy

Author information

Vera Battini http://orcid.org/0000-0002-3513-9593

Maria Antonietta Barbieri http://orcid.org/0000-0002-2019-4696

Carla Carnovale http://orcid.org/0000-0002-4107-196X

Edoardo Spina http://orcid.org/0000-0002-2509-7449

Emilio Clementi http://orcid.org/0000-0001-7333-8270

Maurizio Sessa http://orcid.org/0000-0003-0874-4744

Article

Publisher ID: 12300

DOI: 10.1007/s00415-024-12300-9

PMC ID: 11136777

PubMed ID: 38517522

SO-VID: c9682bc5-9420-4219-8ece-c1ab00f62daa

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 23 December 2023

Date revision received : 1 March 2024

Date accepted : 2 March 2024

Funding

Funded by: Copenhagen University

Open Access :

Open access funding provided by Copenhagen University

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: glucagon-like peptide-1 analogues,dipeptidyl peptidase-4 inhibitors,major cognitive impairment,mild cognitive impairment,older individuals,register-based study

Data availability:

ScienceOpen disciplines: Neurology

Keywords: glucagon-like peptide-1 analogues, dipeptidyl peptidase-4 inhibitors, major cognitive impairment, mild cognitive impairment, older individuals, register-based study

Comparing major and mild cognitive impairment risks in older type-2 diabetic patients: a Danish register-based study on dipeptidyl peptidase-4 inhibitors vs. glucagon-like peptide-1 analogues

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Abstract

Introduction

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Discussion

Supplementary Information

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Karger: Neurology and Neuroscience

Most cited references 37

The Danish National Patient Registry: a review of content, data quality, and research potential

The Danish Civil Registration System.

The Danish National Prescription Registry.

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