PMID- 26989182
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20191210
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 39
IP  - 4
DP  - 2016 Apr
TI  - Diabetic Ketoacidosis With Canagliflozin, a Sodium-Glucose Cotransporter 2 
      Inhibitor, in Patients With Type 1 Diabetes.
PG  - 532-8
LID - 10.2337/dc15-1995 [doi]
AB  - OBJECTIVE: To assess the incidence of serious adverse events (AEs) of diabetic 
      ketoacidosis (DKA) with canagliflozin, a sodium-glucose cotransporter 2 
      inhibitor, as an add-on to insulin in adults with type 1 diabetes. RESEARCH 
      DESIGN AND METHODS: In this 18-week, randomized, double-blind, phase 2 study, 
      patients (N = 351; HbA1c 7.0-9.0% [53-75 mmol/mol]) on multiple daily insulin 
      injections or continuous subcutaneous insulin infusion received canagliflozin 100 
      or 300 mg or placebo once daily. The incidence of ketone-related AEs, defined as 
      any event from a prespecified list of preferred terms (i.e., acidosis, blood 
      ketone body increased, blood ketone body present, DKA, diabetic ketoacidotic 
      hyperglycemic coma, ketoacidosis, ketonemia, ketonuria, ketosis, metabolic 
      acidosis, urine ketone body present), including serious AEs of DKA, was assessed 
      based on AE reports. RESULTS: At week 18, the incidence of any ketone-related AE 
      with canagliflozin 100 and 300 mg was 5.1% (n = 6 of 117) and 9.4% (n = 11 of 
      117), respectively; no patients in the placebo group experienced a ketone-related 
      AE. The incidence of serious AEs of DKA was 4.3% (n = 5 of 117) with 
      canagliflozin 100 mg and 6.0% (n = 7 of 117) with canagliflozin 300 mg; all 
      serious events occurred in the presence of circumstances that are known to 
      potentially precipitate DKA (e.g., infection, insulin pump failure). Among the 12 
      patients with a serious AE of DKA, blood glucose levels ranged from 9.4 to >44.4 
      mmol/L (170 to >800 mg/dL). Baseline characteristics were generally similar in 
      patients with and without a ketone-related AE. CONCLUSIONS: Canagliflozin was 
      associated with an increased incidence of serious AEs of DKA in patients with 
      type 1 diabetes inadequately controlled with insulin. Mitigation strategies are 
      needed for use in future clinical trials to reduce the risk of DKA with 
      canagliflozin treatment in patients with type 1 diabetes.
CI  - (c) 2016 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Peters, Anne L
AU  - Peters AL
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, CA 
      momofmax@mac.com.
FAU - Henry, Robert R
AU  - Henry RR
AD  - Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA 
      University of California, San Diego, La Jolla, CA.
FAU - Thakkar, Payal
AU  - Thakkar P
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Tong, Cindy
AU  - Tong C
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Alba, Maria
AU  - Alba M
AD  - Janssen Research & Development, LLC, Raritan, NJ.
LA  - eng
SI  - ClinicalTrials.gov/NCT02139943
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
CIN - Ann Intern Med. 2016 Jul 19;165(2):JC2. PMID: 27429314
MH  - Adult
MH  - Aged
MH  - Blood Glucose
MH  - Body Mass Index
MH  - Canagliflozin/administration & dosage/*adverse effects
MH  - Diabetes Mellitus, Type 1/*drug therapy
MH  - Diabetic Ketoacidosis/*chemically induced/diagnosis
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Incidence
MH  - Insulin/administration & dosage
MH  - Insulin Infusion Systems
MH  - Male
MH  - Middle Aged
MH  - Sodium-Glucose Transporter 2
MH  - *Sodium-Glucose Transporter 2 Inhibitors
EDAT- 2016/03/19 06:00
MHDA- 2017/10/24 06:00
CRDT- 2016/03/19 06:00
PHST- 2015/09/11 00:00 [received]
PHST- 2016/02/01 00:00 [accepted]
PHST- 2016/03/19 06:00 [entrez]
PHST- 2016/03/19 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
AID - dc15-1995 [pii]
AID - 10.2337/dc15-1995 [doi]
PST - ppublish
SO  - Diabetes Care. 2016 Apr;39(4):532-8. doi: 10.2337/dc15-1995.