Evidence map›Paper›PMID 31858718›Full record

ArticleDiabetes, obesity & metabolism2020

Low-dose empagliflozin as adjunct-to-insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy.

Bruce A Perkins, Nima Soleymanlou, Julio Rosenstock, Jay S Skyler, Lori M Laffel, Karl-Heinz Liesenfeld, Dietmar Neubacher, Matthew M Riggs, Curtis K Johnston, Rena J Eudy-Byrne and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
  2. Latent autoimmune diabetes in youth.Frontiers in immunology · 2025
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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

14 authors at 7 institutions in 3 countries.

Bruce A PerkinsLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Nima SoleymanlouBoehringer Ingelheim Canada Ltd, Burlington, Ontario, Canada.
Julio RosenstockDallas Diabetes Research Center at Medical City, Dallas, Texas, United States.
Jay S SkylerDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States.
Lori M LaffelJoslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States.
Karl-Heinz LiesenfeldBoehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Dietmar NeubacherBoehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Matthew M RiggsMetrum Research Group, Tariffville, Connecticut, United States.
Curtis K JohnstonMetrum Research Group, Tariffville, Connecticut, United States.
Rena J Eudy-ByrneMetrum Research Group, Tariffville, Connecticut, United States.
Ahmed ElmokademMetrum Research Group, Tariffville, Connecticut, United States.
Jyothis T GeorgeBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Jan MarquardBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Valerie NockBoehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Boehringer Ingelheim (Germany) · DEMetrum Research Group (United States) · USBoehringer Ingelheim (Canada) · CADallas Diabetes Research Center · USJoslin Diabetes Center · USUniversity of Miami · USUniversity of Toronto · CA

Funding

Boehringer IngelheimEli Lilly and Company Diabetes Alliance
6 · The paper itself

Abstract

aimTo confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE-3 by modelling and simulation analyses. MATERIALS AND

methodsIndependent of data from EASE-3 that tested 2.5 mg, we simulated the effect of a 2.5 mg dose through patient-level, exposure-response modelling in the EASE-2 clinical study. A primary semi-mechanistic model evaluated efficacy considering clinical insulin dose adjustments made after treatment initiation that potentially limited HbA1c reductions. The model was informed by pharmacokinetic, insulin dose, mean daily glucose and HbA1c data, and was verified by comparing the simulations with the observed HbA1c change in EASE-3. One of two empagliflozin phase 3 trials in type 1 diabetes (EASE-3 but not EASE-2) included a lower 2.5 mg dose. A placebo-corrected HbA1c reduction of 0.28% was demonstrated without the increased risk of diabetic ketoacidosis observed at higher doses (10 mg and 25 mg). Since only one trial included the lower dose, we aimed to confirm the observed reduction in HbA1c for the 2.5 mg dose by modelling and simulation analyses.

resultsThe simulated 26-week mean HbA1c change was -0.41% without insulin dose adjustment and -0.29% at 26 weeks with insulin dose adjustment. A simplified (descriptive) model excluding insulin dose and mean daily glucose confirmed the -0.29% HbA1c change that would have been observed had the EASE-2 population received a 2.5 mg dose for 26/52 weeks.

conclusionsThe HbA1c benefit of low-dose empagliflozin directly observed in the EASE-3 trial was confirmed by two modelling and simulation approaches.

Indexed as

Diabetes Mellitus, Type 1InsulinBenzhydryl CompoundsDose-Response Relationship, DrugDouble-Blind MethodDrug Therapy, CombinationGlucosidesGlycated HemoglobinHumansHypoglycemic AgentsBenzhydryl CompoundsempagliflozinGlucosidesGlycated HemoglobinHypoglycemic AgentsInsulinantidiabetic drugdose-response relationshipempagliflozinsodium-glucose co-transporter-2 inhibitortype 1 diabetes

Identifiers

PMID31858718
PMCPMC7064984
OpenAlexW2996554586

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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 OpenQuestion graph.