PMID- 35472672
OWN - NLM
STAT- MEDLINE
DCOM- 20220606
LR  - 20220716
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 45
IP  - 6
DP  - 2022 Jun 2
TI  - Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney 
      Disease: Pooled Analysis of Placebo-Controlled Clinical Trials.
PG  - 1445-1452
LID - 10.2337/dc21-2034 [doi]
AB  - OBJECTIVE: To 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 METHODS: This 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. RESULTS: 
      Among 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). 
      CONCLUSIONS: Use 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.
CI  - (c) 2022 by the American Diabetes Association.
FAU - Tuttle, Katherine R
AU  - Tuttle KR
AUID- ORCID: 0000-0002-2235-0103
AD  - Providence Health Care, University of Washington, Spokane, WA.
FAU - Levin, Adeera
AU  - Levin A
AD  - University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Nangaku, Masaomi
AU  - Nangaku M
AD  - Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Kadowaki, Takashi
AU  - Kadowaki T
AD  - Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
AD  - Toranomon Hospital, Tokyo, Japan.
FAU - Agarwal, Rajiv
AU  - Agarwal R
AD  - Indiana University, Indianapolis, IN.
FAU - Hauske, Sibylle J
AU  - Hauske SJ
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
AD  - Vth Department of Medicine, University Medical Center Mannheim, University of 
      Heidelberg, Heidelberg, Germany.
FAU - Elsasser, Amelie
AU  - Elsasser A
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Ritter, Ivana
AU  - Ritter I
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Steubl, Dominik
AU  - Steubl D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
AD  - Department of Nephrology, Faculty of Medicine, Technical University Munich, 
      Munich, Germany.
FAU - Wanner, Christoph
AU  - Wanner C
AD  - Wurzburg University Clinic, Wurzburg, Germany.
FAU - Wheeler, David C
AU  - Wheeler DC
AD  - University College London, London, U.K.
LA  - eng
SI  - ClinicalTrials.gov/NCT03594110
SI  - ClinicalTrials.gov/NCT00885118
SI  - ClinicalTrials.gov/NCT00789035
SI  - ClinicalTrials.gov/NCT00558571
SI  - ClinicalTrials.gov/NCT00749190
SI  - ClinicalTrials.gov/NCT01011868
SI  - ClinicalTrials.gov/NCT01193218
SI  - ClinicalTrials.gov/NCT01210001
SI  - ClinicalTrials.gov/NCT01177813
SI  - ClinicalTrials.gov/NCT01159600
SI  - ClinicalTrials.gov/NCT01289990
SI  - ClinicalTrials.gov/NCT01131676
SI  - ClinicalTrials.gov/NCT01164501
SI  - ClinicalTrials.gov/NCT01370005
SI  - ClinicalTrials.gov/NCT01306214
SI  - ClinicalTrials.gov/NCT01649297
SI  - ClinicalTrials.gov/NCT01947855
SI  - ClinicalTrials.gov/NCT02589639
SI  - figshare/10.2337/figshare.19465484
GR  - R01 HL126903/HL/NHLBI NIH HHS/United States
GR  - UC4 DK101108/DK/NIDDK NIH HHS/United States
GR  - U2C DK114886/DK/NIDDK NIH HHS/United States
GR  - U54 DK083912/DK/NIDDK NIH HHS/United States
GR  - UM1 DK100846/DK/NIDDK NIH HHS/United States
GR  - I01 CX001753/CX/CSRD VA/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Benzhydryl Compounds/adverse effects
MH  - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy
MH  - Glucosides
MH  - Humans
MH  - *Hyperkalemia/chemically induced/drug therapy
MH  - Hypoglycemic Agents/therapeutic use
MH  - *Renal Insufficiency, Chronic/drug therapy
PMC - PMC9210861
EDAT- 2022/04/27 06:00
MHDA- 2022/06/07 06:00
PMCR- 2022/04/26
CRDT- 2022/04/26 20:14
PHST- 2021/09/29 00:00 [received]
PHST- 2022/03/25 00:00 [accepted]
PHST- 2022/04/27 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/04/26 20:14 [entrez]
PHST- 2022/04/26 00:00 [pmc-release]
AID - 145036 [pii]
AID - 212034 [pii]
AID - 10.2337/dc21-2034 [doi]
PST - ppublish
SO  - Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.