PMID- 27046479
OWN - NLM
STAT- MEDLINE
DCOM- 20170928
LR  - 20181202
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 32
IP  - 8
DP  - 2016 Aug
TI  - The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on 
      mineral metabolism and bone in patients with type 2 diabetes mellitus.
PG  - 1375-85
LID - 10.1080/03007995.2016.1174841 [doi]
AB  - BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors lower blood 
      glucose levels in patients with type 2 diabetes mellitus (T2DM) by increasing 
      urinary glucose excretion. This review provides a comprehensive summary of 
      preclinical and clinical data on the effects of the SGLT2 inhibitor canagliflozin 
      on mineral balance and bone. METHODS: Published articles and internal study 
      reports through November 2015 were included. RESULTS: In clinical studies, 
      canagliflozin was not associated with meaningful changes in serum or urine 
      calcium, parathyroid hormone, or vitamin D. Canagliflozin was associated with 
      increases in serum magnesium and phosphate without changes in their urinary 
      excretion. Increases in serum collagen type-1 beta-carboxy-telopeptide 
      (beta-CTX), a bone resorption marker, and osteocalcin, a bone formation marker, 
      were observed with canagliflozin. Decreases in total hip bone mineral density 
      (BMD) of up to 1.2% were seen with canagliflozin after 2 years; no changes in BMD 
      were seen at other skeletal sites. Changes in total hip BMD and serum beta-CTX 
      with canagliflozin correlated with decreases in body weight. In a clinical 
      program-wide analysis, canagliflozin was associated with increased fracture risk 
      that was driven by a higher incidence in the cardiovascular safety study 
      (CANVAS), with no fracture imbalance seen in pooled data from other Phase 3 
      studies. The fracture imbalance occurred within 12 weeks after initiating 
      treatment, most frequently in the distal portion of the upper and lower 
      extremities. CONCLUSIONS: Across clinical studies, canagliflozin did not 
      meaningfully affect calcium homeostasis or hormones regulating calcium 
      homeostasis. Increases in bone turnover markers and decreases in BMD at the total 
      hip, but not at other sites, that correlated with weight loss were seen with 
      canagliflozin. Canagliflozin was associated with a higher fracture incidence 
      within 12 weeks, primarily in distal extremities. Data from ongoing canagliflozin 
      studies will provide additional information on fracture risk.
FAU - Alba, Maria
AU  - Alba M
AD  - a Janssen Research & Development, LLC , Raritan , NJ , USA.
FAU - Xie, John
AU  - Xie J
AD  - a Janssen Research & Development, LLC , Raritan , NJ , USA.
FAU - Fung, Albert
AU  - Fung A
AD  - a Janssen Research & Development, LLC , Raritan , NJ , USA.
FAU - Desai, Mehul
AU  - Desai M
AD  - a Janssen Research & Development, LLC , Raritan , NJ , USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160506
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Bone Density/*drug effects
MH  - Bone Remodeling/drug effects
MH  - Calcium/*metabolism
MH  - Canagliflozin/*adverse effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Fractures, Bone/chemically induced
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects
MH  - *Sodium-Glucose Transporter 2 Inhibitors
OTO - NOTNLM
OT  - Bone biomarkers
OT  - Bone mineral density
OT  - Canagliflozin
OT  - Fractures
OT  - SGLT2 inhibitor
OT  - Type 2 diabetes mellitus
EDAT- 2016/04/06 06:00
MHDA- 2017/09/29 06:00
CRDT- 2016/04/06 06:00
PHST- 2016/04/06 06:00 [entrez]
PHST- 2016/04/06 06:00 [pubmed]
PHST- 2017/09/29 06:00 [medline]
AID - 10.1080/03007995.2016.1174841 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2016 Aug;32(8):1375-85. doi: 10.1080/03007995.2016.1174841. 
      Epub 2016 May 6.