Evidence mapPaperPMID 36635409Full record

ArticleScientific reports2023

Linagliptin treatment is associated with altered cobalamin (VitB12) homeostasis in mice and humans.

Harald Tammen, Martin Kömhoff, Denis Delić, Søren S Lund, Berthold Hocher, Sandra Frankenreiter, Rüdiger Hess, Maximilian von Eynatten, Michael Mark, Thomas Klein

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 31% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

10 authors at 4 institutions in 2 countries.

Harald TammenPXBioVisioN GmbH, Feodor-Lynen-Straße 31, 30625, Hannover, Germany. htammen@pxbiovision.com.
Martin KömhoffDepartment of Pediatrics, University Marburg, Marburg, Germany.
Denis DelićBoehringer Ingelheim GmbH & Co. KG, Birkendorfer Str. 65, Biberach, Germany.
Søren S LundBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Berthold HocherFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
Sandra FrankenreiterBoehringer Ingelheim GmbH & Co. KG, Birkendorfer Str. 65, Biberach, Germany.
Rüdiger HessPXBioVisioN GmbH, Feodor-Lynen-Straße 31, 30625, Hannover, Germany.
Maximilian von EynattenBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Michael MarkBoehringer Ingelheim GmbH & Co. KG, Birkendorfer Str. 65, Biberach, Germany.
Thomas KleinBoehringer Ingelheim GmbH & Co. KG, Birkendorfer Str. 65, Biberach, Germany. thomas_1.klein@boehringer-ingelheim.com.
Boehringer Ingelheim (Germany) · DEPXBioVisioN (Germany) · DEHeidelberg University · DEPhilipps University of Marburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used for the treatment of type 2 diabetes, with additional beneficial effects for the kidney. Treatment of mice with linagliptin revealed increased storage of cobalamin (Cbl, Vitamin B12) in organs if a standard Cbl diet (30 µg Cbl/kg chow) is given. In order to translate these findings to humans, we determined methylmalonic acid (MMA), a surrogate marker of functional Cbl homeostasis, in human plasma and urine samples (n = 1092) from baseline and end of trial (6 months after baseline) of the previously completed MARLINA-T2D clinical trial. We found that individuals with medium Cbl levels (MMA between 50 and 270 nmol/L for plasma, 0.4 and 3.5 µmol/mmol creatinine for urine, at baseline and end of trial) exhibited higher MMA values at the end of study in placebo compared with linagliptin. Linagliptin might inhibit the N-terminal degradation of the transcobalamin receptor CD320, which is necessary for uptake of Cbl into endothelial cells. Because we demonstrate that linagliptin led to increased organ levels of Cbl in mice, sustained constant medium MMA levels in humans, and inhibited CD320 processing by DPP-4 in-vitro, we speculate that linagliptin promotes intra-cellular uptake of Cbl by prolonging half-life of CD320.

Indexed as

Diabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsAnimalsEndothelial CellsHomeostasisHumansHypoglycemic AgentsLinagliptinMiceVitamin B 12Dipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsLinagliptinVitamin B 12

Identifiers

PMID36635409
PMCPMC9837112
OpenAlexW4315786202

What Socratic holds

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LicenceCC BY
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Registered trials

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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.