Evidence mapPaperPMID 30968335Full record

ArticleClinical pharmacokinetics2019

Assessment of Drug-Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials.

Katrijn Bogman, Jochen Brumm, Carsten Hofmann, Mylène Giraudon, Markus Niggli, Carolina Sturm-Pellanda, Annette Sauter, Stefan Sturm, Bernhard Mangold, Christophe Schmitt

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. 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 1 institution in 2 countries.

Katrijn BogmanDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland. katrijn.bogman@roche.com.ORCID http://orcid.org/0000-0003-2191-4461
Jochen BrummDepartment of Biostatistics, Genentech, South San Francisco, CA, USA.
Carsten HofmannDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Mylène GiraudonDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Markus NiggliDepartment of Biostatistics, Pharma Development, F. Hoffmann-La Roche AG, Basel, Switzerland.
Carolina Sturm-PellandaDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Annette SauterDepartment of Biostatistics, Pharma Development, F. Hoffmann-La Roche AG, Basel, Switzerland.
Stefan SturmDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Bernhard MangoldDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Christophe SchmittDepartment of Clinical Pharmacology, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, Basel, CH-4070, Switzerland.
Roche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveTaspoglutide, a glucagon-like peptide-1 agonist, like native glucagon-like peptide-1, delays gastric emptying time and prolongs intestinal transit time, which may alter the pharmacokinetics of concomitantly administered oral drugs. The effect of taspoglutide on the pharmacokinetics of five oral drugs commonly used in patients with type 2 diabetes mellitus was assessed in healthy subjects.

methodsFive clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin, and simvastatin and multiple doses of digoxin and an oral contraceptive containing ethinylestradiol and levonorgestrel. The extent of interaction was quantified using geometric mean ratios and 90% confidence intervals for the maximum plasma concentration and area under the plasma concentration-time curve. In addition to pharmacokinetics, pharmacodynamic effects were assessed for warfarin and the oral contraceptive.

resultsAmong the tested drugs, the effect of taspoglutide on the pharmacokinetics of simvastatin was most pronounced, on the day of taspoglutide administration, the average exposure to simvastatin was decreased by - 26% and - 58% for the area under the plasma concentration-time curve and maximum plasma concentration, respectively, accompanied by an increase in average exposure to its active metabolite, simvastatin β-hydroxy acid (+ 74% and + 23% for area under the plasma concentration-time curve and maximum plasma concentration, respectively). Although statistically significant changes in exposure were observed for other test drugs, the 90% confidence intervals for the geometric mean ratio for maximum plasma concentration and area under the plasma concentration-time curve were within the 0.7-1.3 interval. No clinically relevant changes on coagulation (for warfarin) and ovulation-suppressing activity (for the oral contraceptive) were apparent.

conclusionOverall, multiple doses of taspoglutide did not result in changes in the pharmacokinetics of digoxin, an oral contraceptive containing ethinylestradiol and levonorgestrel, lisinopril, warfarin, and simvastatin that would be considered of clinical relevance. Therefore, no dose adjustments are warranted upon co-administration.

Indexed as

Administration, OralAdultAngiotensin-Converting Enzyme InhibitorsAnticholesteremic AgentsAnticoagulantsCardiotonic AgentsCase-Control StudiesContraceptives, OralDiabetes Mellitus, Type 2DigoxinDrug InteractionsFemaleGlucagon-Like Peptide 1Healthy VolunteersHumansInjections, SubcutaneousAngiotensin-Converting Enzyme InhibitorsAnticholesteremic AgentsAnticoagulantsCardiotonic AgentsContraceptives, OralDigoxinGlucagon-Like Peptide 1LisinoprilPeptidesPharmaceutical PreparationsSimvastatintaspoglutideWarfarin

Identifiers

PMID30968335
OpenAlexW2940414042

What Socratic holds

Texttitle and abstract
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.