Evidence mapPaperPMID 21714581Full record

Trial reportClinical drug investigation2011

Effect of multiple oral doses of linagliptin on the steady-state pharmacokinetics of a combination oral contraceptive in healthy female adults: an open-label, two-period, fixed-sequence, multiple-dose study.

Christian Friedrich, Andreas Port, Arne Ring, Ulrike Graefe-Mody, Thomas Giessmann, Mario Iovino, Hans-Juergen Woerle

Abstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in Clinical drug investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

9 citing papers in PubMed, 25 citations in OpenAlex.

  1. Trial
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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

7 authors at 1 institution in 1 country.

Christian FriedrichBoehringer Ingelheim Pharma GmbH Co. KG, Biberach, Germany. Christian.Friedrich@boehringer-ingelheim.com
Andreas Port
Arne Ring
Ulrike Graefe-Mody
Thomas Giessmann
Mario Iovino
Hans-Juergen Woerle
Boehringer Ingelheim (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLinagliptin is an oral dipeptidyl peptidase (DPP)-4 inhibitor that has been recently approved for the treatment of type 2 diabetes mellitus. Microgynon® 30 is a combined oral contraceptive pill containing both ethinylestradiol 30 μg and levonorgestrel 150 μg (EE 30 μg/LNG 150 μg).

objectiveThe objective of this study was to determine the effect of multiple doses of linagliptin (5 mg once daily) on the steady-state pharmacokinetics of EE and LNG following once-daily doses of EE 30 μg/LNG 150 μg.

methodsThis was an open-label, two-period, fixed-sequence, multiple-dose study, consisting of a run-in period, a 14-day reference treatment period and a 7-day test treatment period. The study recruited 18 healthy pre-menopausal female subjects aged 18-40 years with a body mass index of 18.5-27.0 kg/m2. Only women with regular menstrual cycles were included in this study. The treatment sequence was divided into three steps: an individually tailored run-in period with EE 30 μg/LNG 150 μg to synchronize the menstrual cycles of the subjects followed by a washout period of 7 days; the reference treatment period, during which EE 30 μg/LNG 150 μg alone was taken on days 1-14; and the test treatment period, during which EE 30 μg/LNG 150 μg plus linagliptin were taken on days 15-21. The pharmacokinetic parameters measured were maximum steady-state plasma concentration during a dosage interval (C(max,ss)), time to reach maximum plasma concentration following administration at steady state (t(max,ss)) and area under the plasma concentration-time curve during a dosage interval (τ) at steady state (AUC(τ,ss)).

resultsThe AUC(τ,ss) and C(max,ss) of EE and LNG were comparable when EE 30 μg/LNG 150 μg was given alone or combined with linagliptin. The adjusted geometric mean ratios for AUC(τ,ss) and C(max,ss) of EE following EE 30 μg/LNG 150 μg plus linagliptin versus EE 30 μg/LNG 150 μg alone were 101.4 (90% CI 97.2, 105.8) and 107.8 (90% CI 99.7, 116.6), respectively. The adjusted geometric mean ratios for AUC(τ,ss) and C(max,ss) of LNG following EE 30 μg/LNG 150 μg plus linagliptin versus EE 30 μg/LNG 150 μg alone were 108.8 (90% CI 104.5, 113.3) and 113.5 (90% CI 106.1, 121.3), respectively. The combination was well tolerated.

conclusionLinagliptin had no clinically relevant effect on the steady-state pharmacokinetics of EE and LNG in healthy female subjects, and the combination of EE 30 μg/LNG 150 μg and linagliptin was well tolerated in this study. Therefore, linagliptin has the potential to be used in the treatment of female patients with type 2 diabetes in combination with oral contraceptives containing these components, such as EE 30 μg/LNG 150 μg.

trial registrationThe EudraCT number for this study is 2008-000953-37.

Indexed as

AdultArea Under CurveContraceptives, Oral, CombinedDipeptidyl-Peptidase IV InhibitorsDrug CombinationsDrug InteractionsEthinyl EstradiolFemaleHumansLevonorgestrelLinagliptinPurinesQuinazolinesYoung AdultContraceptives, Oral, CombinedDipeptidyl-Peptidase IV InhibitorsDrug CombinationsEthinyl Estradiolethinyl estradiol, levonorgestrel drug combinationLevonorgestrelLinagliptinPurinesQuinazolines

Identifiers

PMID21714581
OpenAlexW345287456

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.