PMID- 27854055
OWN - NLM
STAT- MEDLINE
DCOM- 20170905
LR  - 20210109
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 34
IP  - 1
DP  - 2017 Jan
TI  - Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 
      Diabetes: An Overview.
PG  - 41-59
LID - 10.1007/s12325-016-0434-2 [doi]
AB  - Metformin is recommended as a first-line therapy for patients with type 2 
      diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals 
      with metformin monotherapy and require subsequent combination therapy with other 
      antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood 
      glucose, initial combination therapy may be required to achieve glycemic control. 
      The American Association for Clinical Endocrinologists algorithm for the 
      treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 
      (SGLT2) inhibitor as the first oral combination in patients who present with 
      HbA1c >/=7.5%. Canagliflozin, an SGLT2 inhibitor, lowers the renal threshold for 
      glucose and increases urinary glucose excretion leading to a mild osmotic 
      diuresis and a net caloric loss. The effect of canagliflozin is 
      insulin-independent and complementary to other AHAs, including metformin. A 
      fixed-dose combination (FDC) of canagliflozin and metformin is also available 
      with variable dosing, which may be attractive to some patients owing to the 
      potential for reduced pill burden and costs. This article reviews the efficacy 
      and safety of canagliflozin in combination with metformin based on data from the 
      canagliflozin phase 3 clinical program. As initial combination therapy in 
      drug-naive patients or as dual therapy with metformin or triple therapy in 
      combination with metformin and other AHAs, canagliflozin 100 and 300 mg improved 
      glycemic control and provided reductions in body weight and systolic blood 
      pressure that were sustained for up to 104 weeks. Canagliflozin was generally 
      well tolerated across studies in combination with metformin. An increased 
      incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition 
      (i.e., genital mycotic infections, urinary tract infections, osmotic 
      diuresis-related AEs) was observed with canagliflozin. Canagliflozin was 
      associated with a low incidence of hypoglycemia when not used in conjunction with 
      AHAs associated with hypoglycemia (i.e., insulin or sulfonylurea). Together, 
      these results support the use of a canagliflozin and metformin FDC as a treatment 
      approach for a broad range of patients with T2DM. FUNDING: Janssen Scientific 
      Affairs, LLC.
FAU - Davidson, Jaime A
AU  - Davidson JA
AD  - Department of Medicine, Touchstone Diabetes Center, University of Texas 
      Southwestern Medical Center, Dallas, TX, USA. jaime.davidson@utsouthwestern.edu.
FAU - Sloan, Lance
AU  - Sloan L
AD  - Texas Institute for Kidney and Endocrine Disorders, Lufkin, TX, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20161116
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 9100L32L2N (Metformin)
MH  - Blood Glucose/drug effects
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Canagliflozin/administration & dosage/adverse effects/*therapeutic use
MH  - Clinical Trials, Phase III as Topic
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Glucosides/administration & dosage
MH  - Humans
MH  - Hyperglycemia/drug therapy
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/administration & dosage/*therapeutic use
MH  - Metformin/administration & dosage/adverse effects/*therapeutic use
MH  - Sodium-Glucose Transporter 2 Inhibitors
PMC - PMC5216068
OTO - NOTNLM
OT  - Canagliflozin
OT  - Efficacy
OT  - Endocrinology
OT  - Fixed-dose combination
OT  - Metformin
OT  - Safety
OT  - Sodium glucose co-transporter 2 inhibitors
OT  - Type 2 diabetes mellitus
EDAT- 2016/11/18 06:00
MHDA- 2017/09/07 06:00
PMCR- 2016/11/16
CRDT- 2016/11/18 06:00
PHST- 2016/08/16 00:00 [received]
PHST- 2016/11/18 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2016/11/18 06:00 [entrez]
PHST- 2016/11/16 00:00 [pmc-release]
AID - 10.1007/s12325-016-0434-2 [pii]
AID - 434 [pii]
AID - 10.1007/s12325-016-0434-2 [doi]
PST - ppublish
SO  - Adv Ther. 2017 Jan;34(1):41-59. doi: 10.1007/s12325-016-0434-2. Epub 2016 Nov 16.