Evidence map›Paper›PMID 29766636›Full record

Trial reportDiabetes, obesity & metabolism2018

Empagliflozin as add-on to linagliptin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a 52-week, randomized, placebo-controlled trial.

Ryuzo Kawamori, Masakazu Haneda, Keiko Suzaki, Gang Cheng, Kosuke Shiki, Yuki Miyamoto, Fernando Solimando, Christopher Lee, Jisoo Lee, Jyothis George

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02453555. Cited by 26 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 11 pooled it
3.9field-weighted citation impact, top 5% 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.

NCT02453555 phase3completed

A Phase III, Randomised, Double-blind, Parallel Group, 52 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin and Linagliptin Fixed Dose Combination Compared With Linagliptin Plus Placebo in Japanese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control After 16 Weeks Treatment With Once Daily Linagliptin 5 mg.

Ran2015Enrolled275Registered outcomes5Posted comparisons4ConditionsDiabetes Mellitus, Type 2ArmsEmpagliflozin + linagliptin high dose, Empagliflozin + linagliptin low dose, Empagliflozin placebo + linagliptin placebo low dose, Empa + lina highdose placebo, Linagliptin
Open the trial in the graph
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 11 syntheses or guidelines pooled it, 41 citations in OpenAlex.

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  16. Fixed-Dose Combination Therapy as a Strategy to Improve Antidiabetic Medication Adherence in People with Type 2 Diabetes: A Narrative Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
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  19. Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022
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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

10 authors at 6 institutions in 4 countries.

Ryuzo KawamoriSportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Masakazu HanedaDivision of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Keiko SuzakiNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Gang ChengBoehringer Ingelheim (China) Investment Co. Ltd, Shanghai, China.
Kosuke ShikiNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Yuki MiyamotoNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Fernando SolimandoBoehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
Christopher LeeBoehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
Jisoo LeeBoehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
Jyothis GeorgeBoehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
Boehringer Ingelheim (Germany) · DEBoehringer Ingelheim (Philippines) · PHAsahikawa Medical University · JPBoehringer Ingelheim (China) · CNBoehringer Ingelheim (Japan) · JPJuntendo University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov NCT02453555) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg as add-on to linagliptin (Lina) 5 mg (fixed-dose combination, Empa/Lina 10/5 or 25/5) in insufficiently controlled Japanese type 2 diabetes patients.

methodsThe trial (40 sites; May 2015-March 2017) involved screening 433 adults (≥20 years) who were treatment-naive or were using one oral antidiabetic drug for ≥12 weeks, which was discontinued at enrolment. Patients with HbA1c 7.5%-10.0% after ≥16 weeks of using Lina (pre-enrolment or during a 16-week, open-label period) and 2 weeks of using placebo (Plc) for Empa/Lina 10/5, plus Lina, were randomized (2:1) to once-daily Empa/Lina 10/5 (n = 182) or Plc/Lina 10/5 (n = 93) for 24 weeks. Patients with HbA1c ≥ 7.0% at Week 24 received Empa/Lina up-titrated to 25/5 (n = 126) or the corresponding placebo (n = 80), per randomization, from Week 28; 172 Empa/Lina and 84 Plc/Lina patients completed 52 weeks.

resultsChange from baseline in HbA1c was greater (P < .0001) with Empa/Lina than with Plc/Lina at Week 24 (primary outcome, -0.93% vs 0.21%; adjusted mean difference, -1.14%) and Week 52 (-1.16% vs 0.06%; adjusted mean difference, -1.22%). More patients with HbA1c < 7.0% and greater decreases in fasting plasma glucose, body weight and systolic blood pressure were seen in the Empa/Lina group than in the Plc/Lina group. Empa/Lina was well tolerated. The adverse events that were more frequent with Empa/Lina were known empagliflozin-associated events (eg, increased urination, increased blood ketones). There were no adjudication-confirmed diabetic ketoacidosis events or lower limb amputations.

conclusionsThese results support the notion that empagliflozin-linagliptin in fixed-dose combination is a therapeutic option for Japanese patients with type 2 diabetes.

Indexed as

AgedBenzhydryl CompoundsBlood GlucoseBody WeightDiabetes Mellitus, Type 2Double-Blind MethodDrug Therapy, CombinationFemaleGlucosidesGlycated HemoglobinHumansHypoglycemic AgentsLinagliptinMaleMiddle AgedTreatment OutcomeBenzhydryl CompoundsBlood GlucoseempagliflozinGlucosidesGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsLinagliptinempagliflozinglycaemic controllinagliptinphase III studyrandomized trialtype 2 diabetes

Identifiers

PMID29766636
PMCPMC6099460
OpenAlexW2805665588

What Socratic holds

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LicenceCC BY-NC
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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.