Evidence mapPaperPMID 19476474Full record

Trial reportDiabetes, obesity & metabolism2009

Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients.

T Heise, E U Graefe-Mody, S Hüttner, A Ring, D Trommeshauser, K A Dugi

2 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
field-weighted citation impact
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.

NCT03004612 phase4completedstarted 2016, after this paper: background citation

Effect of Linagliptin + Metformin vs Metformin Alone on the Role of Pancreatic Islet Function, Insulin Resistance and Markers of Cardiovascular Risk in Patients With Prediabetes: Randomized Clinical Trial

Ran2016Enrolled144Registered outcomes5Posted comparisons0ConditionsInsulin Resistance, Prediabetic StateArmsLinagliptin + metformin, Metformin
Open the trial in the graph
NCT04542213 phase3completednot on this mapstarted 2020, after this paper: background citation

Effect of the Combination of Dipeptidyl Peptidase-4 Inhibitor (DPP4i) and Insulin in Comparison to Insulin on Metabolic Control and Prognosis in Hospitalized Patients With COVID-19

TypeinterventionalSponsorHospital Regional de Alta Especialidad del BajioRan2020 to 2021Enrolled70ConditionsHyperglycemia, Covid19ArmsLinagliptin tablet, Insulin
3 · Its place in the literature

Who cites it

63 citing papers in PubMed.

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3 more citing papers are in PubMed but not listed here.

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

6 authors.

T HeiseProfil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse, Neuss, Germany.
E U Graefe-Mody
S Hüttner
A Ring
D Trommeshauser
K A Dugi

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo investigate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of multiple oral doses of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (BI 1356) in patients with type 2 diabetes mellitus.

methodsForty-seven male type 2 diabetic patients received linagliptin 1, 2.5, 5 or 10 mg, or placebo, once daily for 12 days.

resultsLinagliptin exposure [area under the plasma concentration-time curve and maximum plasma concentration (Cmax)] increased less than proportionally with dose. Accumulation half-life was short (8.6-23.9 h), resulting in rapid attainment of steady state (2-5 days) and little accumulation (range: 1.18-2.03). The long terminal half-life (113-131 h) led to a sustained inhibition of DPP-4 activity. Renal excretion was below 1% on day 1 in all dose groups. Inhibition of plasma DPP-4 activity correlated well with linagliptin plasma concentrations, resulting in DPP-4 inhibition >90% in the two highest dose groups; even 24 h postdose, DPP-4 inhibition was >80%. Following an oral glucose tolerance test, 24 h after the last dose, statistically significant reductions of glucose excursions were observed with linagliptin (2.5, 5 and 10 mg doses) compared with placebo. Linagliptin was well tolerated. The frequency of adverse events (AEs) was not higher with linagliptin (54%) than with placebo (75%). No serious AEs and no episodes of hypoglycaemia were reported.

conclusionsIn type 2 diabetic patients, multiple rising doses of linagliptin were well tolerated and resulted in significant improvements of glucose parameters. Together with the favourable pharmacokinetics, these results confirm the unique profile of linagliptin in the DPP-4 inhibitor class.

Indexed as

Administration, OralAdultArea Under CurveDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDose-Response Relationship, DrugDouble-Blind MethodHalf-LifeHumansLinagliptinMaleMetabolic Clearance RateMiddle AgedPurinesQuinazolinesDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsLinagliptinPurinesQuinazolines

Identifiers

What Socratic holds

Textmetadata
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.