PMID- 26786577
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 39
IP  - 3
DP  - 2016 Mar
TI  - Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each 
      Component as Monotherapy for Drug-Naive Type 2 Diabetes.
PG  - 353-62
LID - 10.2337/dc15-1736 [doi]
AB  - OBJECTIVE: This study assessed the efficacy/safety of canagliflozin (CANA), a 
      sodium-glucose cotransporter 2 (SGLT2) inhibitor, plus metformin extended-release 
      (MET) initial therapy in drug-naive type 2 diabetes. RESEARCH DESIGN AND METHODS: 
      This 26-week, double-blind, phase 3 study randomized 1,186 patients to CANA 100 
      mg (CANA100)/MET, CANA 300 mg (CANA300)/MET, CANA100, CANA300, or MET. Primary 
      end point was change in HbA(1c) at week 26 for combinations versus monotherapies. 
      Secondary end points included noninferiority in HbA(1c) lowering with CANA 
      monotherapy versus MET; changes in fasting plasma glucose, body weight, and blood 
      pressure; and proportion of patients achieving HbA(1c) <7.0% (<53 mmol/mol). 
      RESULTS: From mean baseline HbA(1c) of 8.8% (73 mmol/mol), CANA100/MET and 
      CANA300/MET significantly lowered HbA(1c) versus MET (median dose, 2,000 mg/day) 
      by -1.77%, -1.78%, and -1.30% (-19.3, -19.5, and -14.2 mmol/mol; differences of 
      -0.46% and -0.48% [-5.0 and -5.2 mmol/mol]; P = 0.001) and versus CANA100 and 
      CANA300 by -1.37% and -1.42% (-15.0 and -15.5 mmol/mol; differences of -0.40% and 
      -0.36% [-4.4 and -3.9 mmol/mol]; P = 0.001). CANA100 and CANA300 monotherapy met 
      noninferiority for HbA(1c) lowering and had significantly more weight loss versus 
      MET (-2.8, -3.7, and -1.9 kg [-3.0%, -3.9%, and -2.1%]; P = 0.016 and P = 0.002). 
      Greater attainment of HbA(1c) <7.0% (50%, 57%, and 43%) and significantly more 
      weight loss (-3.2, -3.9, and -1.9 kg [-3.5%, -4.2%, and -2.1%]; P = 0.001) 
      occurred with CANA100/MET and CANA300/MET versus MET. The incidence of adverse 
      events (AEs) related to SGLT2 inhibition (genital mycotic infections, osmotic 
      diuresis- and volume depletion-related AEs) was higher in the CANA arms 
      (0.4-4.4%) versus MET (0-0.8%). AE-related discontinuation rates were 1.3-3.0% 
      across groups. The incidence of hypoglycemia was 3.0-5.5% in the CANA arms and 
      4.6% with MET. CONCLUSIONS: Initial therapy with CANA plus MET was more effective 
      and generally well tolerated versus each monotherapy in drug-naive type 2 
      diabetes. CANA monotherapy demonstrated noninferior HbA1c lowering versus MET.
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 - Rosenstock, Julio
AU  - Rosenstock J
AD  - Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX 
      juliorosenstock@dallasdiabetes.com.
FAU - Chuck, Leonard
AU  - Chuck L
AD  - Diablo Clinical Research, Walnut Creek, CA.
FAU - Gonzalez-Ortiz, Manuel
AU  - Gonzalez-Ortiz M
AD  - Institute of Experimental and Clinical Therapeutics, Physiology Department, 
      Health Science University Center, University of Guadalajara, Guadalajara, Mexico.
FAU - Merton, Kate
AU  - Merton K
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Craig, Jagriti
AU  - Craig J
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Capuano, George
AU  - Capuano G
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Qiu, Rong
AU  - Qiu R
AD  - Janssen Research & Development, LLC, Raritan, NJ.
LA  - eng
SI  - ClinicalTrials.gov/NCT01809327
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160119
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Glucose/drug effects
MH  - Canagliflozin/*administration & dosage/therapeutic use
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Double-Blind Method
MH  - Female
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/therapeutic use
MH  - Male
MH  - Metformin/*administration & dosage/therapeutic use
MH  - Middle Aged
MH  - Sodium-Glucose Transporter 2 Inhibitors
EDAT- 2016/01/21 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/01/21 06:00
PHST- 2015/08/07 00:00 [received]
PHST- 2015/12/17 00:00 [accepted]
PHST- 2016/01/21 06:00 [entrez]
PHST- 2016/01/21 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - dc15-1736 [pii]
AID - 10.2337/dc15-1736 [doi]
PST - ppublish
SO  - Diabetes Care. 2016 Mar;39(3):353-62. doi: 10.2337/dc15-1736. Epub 2016 Jan 19.