Evidence mapPaperPMID 33918261Full record

ArticlePharmaceutics2021

A Model-Informed Drug Development (MIDD) Approach for a Low Dose of Empagliflozin in Patients with Type 1 Diabetes.

Curtis K Johnston, Rena J Eudy-Byrne, Ahmed Elmokadem, Valerie Nock, Jan Marquard, Nima Soleymanlou, Matthew M Riggs, Karl-Heinz Liesenfeld

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. 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
0.6field-weighted citation impact, top 32% 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, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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 3 institutions in 2 countries.

Curtis K JohnstonMetrum Research Group, Tariffville, CT 06081, USA.
Rena J Eudy-ByrneMetrum Research Group, Tariffville, CT 06081, USA.
Ahmed ElmokademMetrum Research Group, Tariffville, CT 06081, USA.ORCID 0000-0002-2412-4986
Valerie NockBoehringer Ingelheim International GmbH, 55216 Ingelheim, Germany.ORCID 0000-0001-7234-6447
Jan MarquardBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
Nima SoleymanlouBoehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
Matthew M RiggsMetrum Research Group, Tariffville, CT 06081, USA.ORCID 0000-0001-5542-6058
Karl-Heinz LiesenfeldBoehringer Ingelheim International GmbH, 55216 Ingelheim, Germany.
Metrum Research Group (United States) · USBoehringer Ingelheim (Germany) · DEBoehringer Ingelheim (United States) · US

Funding

Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance N/A
6 · The paper itself

Abstract

In clinical trials, sodium-glucose co-transporter (SGLT) inhibitor use as adjunct to insulin therapy in type 1 diabetes (T1D) provides glucometabolic benefits while diabetic ketoacidosis risk is increased. The SGLT2 inhibitor empagliflozin was evaluated in two phase III trials: EASE-2 and EASE-3. A low, 2.5-mg dose was included in EASE-3 only. As the efficacy of higher empagliflozin doses (i.e., 10 and 25 mg) in T1D has been established in EASE-2 and EASE-3, a modeling and simulation approach was used to generate additional supportive evidence on efficacy for the 2.5-mg dose. We present the methodology behind the development and validation of two modeling and simulation frameworks: M-EASE-1, a semi-mechanistic model integrating information on insulin, glucose, and glycated hemoglobin; and M-EASE-2, a descriptive model informed by prior information. Both models were developed independently of data from EASE-3. Simulations based on these models assessed efficacy in untested clinical trial scenarios. In this manner, the models provide supportive evidence for efficacy of low-dose empagliflozin 2.5 mg in patients with T1D, illustrating how pharmacometric analyses can support efficacy assessments in the context of limited data.

Indexed as

Bayesian modelingclinical trial simulationsSGLT2 inhibitorsupportive evidencetype 1 diabetes

Identifiers

PMID33918261
PMCPMC8066500
OpenAlexW3151725768

What Socratic holds

Textmetadata
LicenceCC BY
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.