Evidence mapPaperPMID 30091172Full record

Trial reportDiabetes, obesity & metabolism2019

Linagliptin as add-on to empagliflozin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a two-part, randomized, placebo-controlled trial.

Kohei Kaku, Masakazu Haneda, Yuko Tanaka, Ganghyuck Lee, Kosuke Shiki, Yuki Miyamoto, Fernando Solimando, Jisoo Lee, Christopher Lee, Jyothis George

Registry-linked trialAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02489968. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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.

NCT02489968 phase3completed

A Phase III, Randomised, Double-blind, Parallel Group, 24-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 10 mg Plus Placebo and a 52-week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin 25 mg and Linagliptin 5 mg Fixed Dose Combination Compared With Empagliflozin 25 mg Plus Placebo in Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control After 16-week Treatment With Empagliflozin (10 mg or 25 mg) Alone Once Daily.

Ran2015Enrolled880Registered outcomes1Posted comparisons2ConditionsDiabetes Mellitus, Type 2Armsempagliflozin 10 mg, empagliflozin 10 mg + linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 25 mg + linagliptin 5 mg, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. 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
    Article
  4. 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.

Kohei KakuKawasaki Medical School, Kurashiki, Japan.ORCID 0000-0003-1574-0565
Masakazu HanedaAsahikawa Medical University, Asahikawa, Hokkaido, Japan.
Yuko TanakaNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.ORCID 0000-0002-0804-5807
Ganghyuck LeeNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Kosuke ShikiNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Yuki MiyamotoNippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
Fernando SolimandoBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Jisoo LeeBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Christopher LeeBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Jyothis GeorgeBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis two-part, double-blind, double-dummy, randomized, placebo-controlled trial (83 sites) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg and linagliptin (Lina) 5 mg fixed-dose combinations (FDCs) in Japanese patients with type 2 diabetes mellitus (T2DM) who were poorly controlled with Empa. MATERIALS AND

methodsPatients (previously drug-naive or using one oral antidiabetic drug for ≥ 12 weeks) entered an open-label stabilization period (16 weeks, Empa 10 mg [Part A] or Empa 25 mg [Part B]). Subsequently, they received Empa 10 mg plus placebo (Plc) for Empa/Lina10/5 (Empa/Plc 10/5; Part A) or Empa 25 mg plus Plc for Empa/Lina 25/5 (Empa/Plc 25/5; Part B) for 2 weeks. Patients with HbA1c 7.5-10.0% were randomized (1:1) to a 24-week regimen of once-daily Empa/Lina 10/5 (n = 107) or Empa/Plc 10/5 (n = 108) in Part A, or to Empa/Lina 25/5 (n = 116) or Empa/Plc 25/5 (n = 116) in Part B, with a 28-week extension period in Part B.

resultsChange from baseline in HbA1c at Week 24 was greater (P < 0.0001) with Empa/Lina than with Empa/Plc (primary outcome, Empa/Lina 10/5: -0.94 vs -0.12%; adjusted mean difference, -0.82%; Empa/Lina 25/5: -0.91 vs -0.33%; adjusted mean difference, -0.59%). Over 24- and 52-week periods, higher proportions of patients achieved HbA1c < 7.0% and greater decreases in fasting plasma glucose were observed with Empa/Lina compared with Empa/Plc. Empa/Lina was well tolerated, with no unexpected adverse events or diabetic ketoacidosis. One case of confirmed hypoglycaemia with Empa/Plc 25/5 was reported.

conclusionsThese results support Empa/Lina FDC as a potential option for Japanese patients with T2DM who require combination therapy. ClinicalTrials.gov NCT02489968.

Indexed as

Benzhydryl CompoundsGlucosidesHypoglycemic AgentsLinagliptinAdultAgedBlood GlucoseDiabetes Mellitus, Type 2Drug CombinationsFemaleHumansJapanMaleMiddle AgedBenzhydryl CompoundsBlood GlucoseDrug CombinationsempagliflozinGlucosidesHypoglycemic AgentsLinagliptinempagliflozinglycaemic controllinagliptinphase III studyrandomized trialtype 2 diabetes

Identifiers

PMID30091172
PMCPMC6585831

What Socratic holds

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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.