PMID- 27160639
OWN - NLM
STAT- MEDLINE
DCOM- 20171107
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 18
IP  - 8
DP  - 2016 Aug
TI  - Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes 
      mellitus inadequately controlled on metformin and sitagliptin.
PG  - 812-9
LID - 10.1111/dom.12684 [doi]
AB  - AIMS: To evaluate the efficacy and safety of titrated canagliflozin, a sodium 
      glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus 
      (T2DM) inadequately controlled on metformin and sitagliptin. METHODS: In this 
      randomized, double-blind study, patients with T2DM (N = 218) on metformin >/=1500 
      mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo. After 6 
      weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo 
      to matching placebo) if all of the following criteria were met: baseline 
      estimated glomerular filtration rate >/=70 ml/min/1.73 m(2) ; fasting 
      self-monitored blood glucose >/=5.6 mmol/l (>/=100 mg/dl); and no volume 
      depletion-related adverse events (AEs) within 2 weeks before dose increase. 
      Endpoints included change in glycated haemoglobin (HbA1c) at week 26 (primary); 
      proportion of patients achieving HbA1c <7.0%; and changes in fasting plasma 
      glucose (FPG), body weight and systolic blood pressure (SBP). Safety was assessed 
      using AE reports. RESULTS: Overall, 85.4% of patients were titrated to 
      canagliflozin 300 mg or matching placebo (mean +/- standard deviation time to 
      titration 6.2 +/- 0.8 weeks). At week 26, canagliflozin (pooled 100 and 300 mg) 
      demonstrated superiority in HbA1c reduction versus placebo (-0.91% vs. -0.01%; p 
      < 0.001). Canagliflozin provided significant reductions in FPG, body weight and 
      SBP compared with placebo (p < 0.001). The overall AE incidence was 39.8 and 
      44.4% for canagliflozin and placebo, respectively. Canagliflozin was associated 
      with an increased incidence of genital mycotic infections. CONCLUSIONS: Titrated 
      canagliflozin significantly improved HbA1c, FPG, body weight and SBP, and was 
      generally well tolerated over 26 weeks in patients with T2DM as add-on to 
      metformin and sitagliptin.
CI  - (c) 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Rodbard, H W
AU  - Rodbard HW
AD  - Endocrine and Metabolic Consultants, Rockville, MD, USA.
FAU - Seufert, J
AU  - Seufert J
AD  - Department of Endocrinology and Diabetology, Clinic for Internal Medicine II, 
      University Medical Center, Freiburg, Germany.
FAU - Aggarwal, N
AU  - Aggarwal N
AD  - Aggarwal and Associates Ltd, Brampton, ON, Canada.
FAU - Cao, A
AU  - Cao A
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
FAU - Fung, A
AU  - Fung A
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
FAU - Pfeifer, M
AU  - Pfeifer M
AD  - Janssen Scientific Affairs, LLC, Raritan, NJ, USA.
FAU - Alba, M
AU  - Alba M
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160607
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 9100L32L2N (Metformin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Aged
MH  - Blood Glucose/metabolism
MH  - Blood Pressure
MH  - Body Weight
MH  - Canagliflozin/*therapeutic use
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Hypovolemia/chemically induced
MH  - Male
MH  - Metformin/*therapeutic use
MH  - Middle Aged
MH  - Mycoses/chemically induced
MH  - Reproductive Tract Infections/chemically induced
MH  - Sitagliptin Phosphate/*therapeutic use
MH  - Treatment Failure
MH  - Treatment Outcome
MH  - Urinary Tract Infections/chemically induced
PMC - PMC5089595
OTO - NOTNLM
OT  - canagliflozin
OT  - sitagliptin
OT  - sodium glucose co-transporter
OT  - titration
OT  - triple therapy
OT  - type 2 diabetes mellitus
EDAT- 2016/05/11 06:00
MHDA- 2017/11/08 06:00
PMCR- 2016/11/01
CRDT- 2016/05/11 06:00
PHST- 2016/03/21 00:00 [received]
PHST- 2016/04/11 00:00 [revised]
PHST- 2016/05/01 00:00 [accepted]
PHST- 2016/05/11 06:00 [entrez]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2017/11/08 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - DOM12684 [pii]
AID - 10.1111/dom.12684 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2016 Aug;18(8):812-9. doi: 10.1111/dom.12684. Epub 2016 Jun 
      7.