PMID- 32928957
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20210520
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 43
IP  - 11
DP  - 2020 Nov
TI  - Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in 
      Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies.
PG  - 2713-2720
LID - 10.2337/dc20-0924 [doi]
AB  - OBJECTIVE: To evaluate the incidence and risk factors for diabetic ketoacidosis 
      (DKA) and related adverse events (AEs) in adults with type 1 diabetes treated 
      with sotagliflozin adjunctive to insulin. RESEARCH DESIGN AND METHODS: Data from 
      two identically designed, 52-week, randomized studies were pooled and analyzed 
      for DKA, changes in beta-hydroxybutyrate (BHB), and percentage of patients with BHB 
      >0.6 and >1.5 mmol/L. The patients were administered placebo, sotagliflozin 200 
      mg, or sotagliflozin 400 mg once daily. RESULTS: A total of 191 ketosis-related 
      AEs were reported, and 98 underwent adjudication. Of these, 37 events (36 
      patients) were adjudicated as DKA, with an exposure-adjusted incidence rate of 
      0.2, 3.1, and 4.2 events per 100 patient-years for placebo, sotagliflozin 200 mg, 
      and sotagliflozin 400 mg, respectively. No patient died of a DKA event. From a 
      baseline BHB of  approximately 0.13 mmol/L, sotagliflozin treatment led to a small median 
      increase over 52 weeks (</=0.05 mmol/L at all time points). Of 
      sotagliflozin-treated patients, approximately 47% and 7% had >/=1 BHB measurement 
      >0.6 mmol/L and >1.5 mmol/L, respectively (vs. 20% and 2%, respectively, of 
      placebo-treated patients). Subsequent to the implementation of a risk mitigation 
      plan, annualized DKA incidence was lower versus preimplementation in both the 
      sotagliflozin 200 and 400 mg groups. CONCLUSIONS: In patients with type 1 
      diabetes, confirmed DKA incidence increased when sotagliflozin was added to 
      insulin compared with insulin alone. A lower incidence of DKA was observed 
      following the implementation of an enhanced risk mitigation plan, suggesting that 
      this risk can be managed with patient education.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Peters, Anne L
AU  - Peters AL
AUID- ORCID: 0000-0003-0520-0776
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, CA 
      annepete@med.usc.edu.
FAU - McGuire, Darren K
AU  - McGuire DK
AUID- ORCID: 0000-0002-6412-7989
AD  - University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
FAU - Danne, Thomas
AU  - Danne T
AUID- ORCID: 0000-0003-0773-6961
AD  - Kinder Krakenhaus auf der Bult, Diabetes Zentrum fur Kinder and Jugendliche, 
      Hannover, Germany.
FAU - Kushner, Jake A
AU  - Kushner JA
AUID- ORCID: 0000-0002-3646-1744
AD  - McNair Interests, Houston, TX.
FAU - Rodbard, Helena W
AU  - Rodbard HW
AUID- ORCID: 0000-0002-6187-8445
AD  - Endocrine and Metabolic Consultants Research Center, Rockville, MD.
FAU - Dhatariya, Ketan
AU  - Dhatariya K
AUID- ORCID: 0000-0003-3619-9579
AD  - Norfolk and Norwich University Hospitals National Health Service Foundation 
      Trust, Norwich, U.K.
FAU - Sawhney, Sangeeta
AU  - Sawhney S
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
FAU - Banks, Phillip
AU  - Banks P
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
FAU - Jiang, Wenjun
AU  - Jiang W
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
FAU - Davies, Michael J
AU  - Davies MJ
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
FAU - Lapuerta, Pablo
AU  - Lapuerta P
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
LA  - eng
SI  - figshare/10.2337/figshare.12824342
SI  - ClinicalTrials.gov/NCT02384941
SI  - ClinicalTrials.gov/NCT02421510
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200914
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Glycosides)
RN  - 0 (Insulin, Regular, Human)
RN  - 0 (SLC5A1 protein, human)
RN  - 0 (Sodium-Glucose Transporter 1)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 6B4ZBS263Y 
      ((2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol)
RN  - TZP1275679 (3-Hydroxybutyric Acid)
SB  - IM
MH  - 3-Hydroxybutyric Acid/blood
MH  - Adult
MH  - Diabetes Mellitus, Type 1/*drug therapy
MH  - Diabetic Ketoacidosis/blood/*chemically induced/*epidemiology
MH  - Double-Blind Method
MH  - Drug Therapy, Combination/adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Glycosides/administration & dosage/*adverse effects
MH  - Humans
MH  - Incidence
MH  - Insulin, Regular, Human/*administration & dosage
MH  - Male
MH  - Sodium-Glucose Transporter 1/*antagonists & inhibitors
MH  - Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/*adverse effects
MH  - Treatment Outcome
PMC - PMC7576419
EDAT- 2020/09/16 06:00
MHDA- 2021/05/21 06:00
PMCR- 2020/09/14
CRDT- 2020/09/15 05:41
PHST- 2020/04/23 00:00 [received]
PHST- 2020/08/09 00:00 [accepted]
PHST- 2020/09/16 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2020/09/15 05:41 [entrez]
PHST- 2020/09/14 00:00 [pmc-release]
AID - dc20-0924 [pii]
AID - 200924 [pii]
AID - 10.2337/dc20-0924 [doi]
PST - ppublish
SO  - Diabetes Care. 2020 Nov;43(11):2713-2720. doi: 10.2337/dc20-0924. Epub 2020 Sep 
      14.