Evidence mapPaperPMID 35472672Full record

Trial reportDiabetes care2022

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials.

Katherine R Tuttle, Adeera Levin, Masaomi Nangaku, Takashi Kadowaki, Rajiv Agarwal, Sibylle J Hauske, Amelie Elsäßer, Ivana Ritter, Dominik Steubl, Christoph Wanner and 1 more

Open access · bronzeAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 9 pooled it
5.3field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 9 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Guideline
  2. Pooled it
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  9. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  10. Trial
  11. Article
  12. Article
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  18. Review
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  20. The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    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

11 authors at 8 institutions in 5 countries.

Katherine R TuttleProvidence Health Care, University of Washington, Spokane, WA.ORCID 0000-0002-2235-0103
Adeera LevinUniversity of British Columbia, Vancouver, British Columbia, Canada.
Masaomi NangakuGraduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi KadowakiGraduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Rajiv AgarwalIndiana University, Indianapolis, IN.
Sibylle J HauskeBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Amelie ElsäßerBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Ivana RitterBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Dominik SteublBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Christoph WannerWürzburg University Clinic, Würzburg, Germany.
David C WheelerUniversity College London, London, U.K.
Boehringer Ingelheim (Germany) · DEThe University of Tokyo · JPToranomon Hospital · JPUniversitätsklinikum Würzburg · DEUniversity College London · GBUniversity of British Columbia · CAUniversity of Indianapolis · USUniversity of Washington · US

Funding

CSRD VA I01 CX001753NHLBI NIH HHS R01 HL126903NIDDK NIH HHS U2C DK114886NIDDK NIH HHS U54 DK083912NIDDK NIH HHS UC4 DK101108NIDDK NIH HHS UM1 DK100846
6 · The paper itself

Abstract

objectiveTo assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials. RESEARCH DESIGN AND

methodsThis analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models.

resultsAmong a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37-0.96, P = 0.0323] and 0.48 [0.26-0.91, P = 0.0243], respectively) and edema (0.47 [0.33-0.68, P < 0.0001] and 0.44 [0.28-0.68, P = 0.0002], respectively).

conclusionsUse of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.

Indexed as

Diabetes Mellitus, Type 2HyperkalemiaRenal Insufficiency, ChronicBenzhydryl CompoundsGlucosidesHumansHypoglycemic AgentsBenzhydryl CompoundsempagliflozinGlucosidesHypoglycemic Agents

Identifiers

PMID35472672
PMCPMC9210861
OpenAlexW4226263934

What Socratic holds

Textmetadata
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.