Evidence mapPaperPMID 33559704Full record

Trial reportDiabetologia2021

Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study.

Geert Jan Biessels, Chloë Verhagen, Jolien Janssen, Esther van den Berg, Gudrun Wallenstein, Bernard Zinman, Mark A Espeland, Odd Erik Johansen

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01243424 (A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.), which is not on this map. Cited by 22 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 3 pooled it
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01243424 phase3completednot on this map

A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.

TypeinterventionalSponsorBoehringer IngelheimRan2010 to 2018Enrolled6,103ConditionsDiabetes Mellitus, Type 2Armslinagliptin, glimepiride, linagliptin placebo, glimepiride placebo
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.

  1. Pooled it
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  4. Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
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  17. What have clinical trials taught us about brain health?Cerebral circulation - cognition and behavior · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 5 countries.

Geert Jan BiesselsDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands. G.J.Biessels@umcutrecht.nl.
Chloë VerhagenDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Jolien JanssenDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Esther van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Gudrun WallensteinBiostatistics and Data Sciences, Boehringer Ingelheim, Ingelheim, Germany.
Bernard ZinmanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Mark A EspelandDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Odd Erik JohansenTherapeutic Area Cardiometabolism, Boehringer Ingelheim, Asker, Norway. odd_erikj@hotmail.com.ORCID http://orcid.org/0000-0003-2470-0530
University Medical Center Utrecht · NLBoehringer Ingelheim (Germany) · DEBoehringer Ingelheim (Norway) · NOErasmus MC · NLMount Sinai Hospital · CAWake Forest University · US

Funding

NIA NIH HHS P30 AG049638
6 · The paper itself

Abstract

aims/hypothesisType 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes.

methodsThe CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA

resultsOf 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA CONCLUSIONS/

interpretationIn a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years.

fundingThis study was sponsored by Boehringer Ingelheim.

trial registrationClinicalTrials.gov NCT01243424.

Indexed as

AgedBlood GlucoseCognitionDiabetes Mellitus, Type 2Double-Blind MethodFemaleHumansHypoglycemic AgentsLinagliptinMaleMiddle AgedNeuropsychological TestsSulfonylurea CompoundsTreatment OutcomeBlood GlucoseglimepirideHypoglycemic AgentsLinagliptinSulfonylurea CompoundsCardiovascular diseaseCognitive declineDPP-4 inhibitorsSulfonylureasType 2 diabetes

Identifiers

PMID33559704
PMCPMC8099814
OpenAlexW3127426737

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.