PMID- 27894216
OWN - NLM
STAT- MEDLINE
DCOM- 20170206
LR  - 20220408
IS  - 1941-9260 (Electronic)
IS  - 0032-5481 (Linking)
VI  - 129
IP  - 1
DP  - 2017 Jan
TI  - Bone effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in 
      patients with type 2 diabetes mellitus.
PG  - 159-168
LID - 10.1080/00325481.2017.1256747 [doi]
AB  - Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for 
      the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by 
      inhibiting renal glucose reabsorption and increasing urinary glucose excretion. 
      It has been reported that SGLT2 inhibitors may have potential adverse effects on 
      bone, including increased fracture risk and decreased bone mineral density (BMD). 
      Across clinical studies, canagliflozin was not associated with meaningful changes 
      in serum or urine calcium, vitamin D, or parathyroid hormone. Minimal increases 
      in serum phosphate and magnesium that were within normal limits were seen with 
      canagliflozin versus placebo. Canagliflozin was associated with increases in 
      serum collagen type 1 beta-carboxy telopeptide (beta-CTX), a bone resorption 
      marker, and osteocalcin, a bone formation marker. Decreases in total hip BMD were 
      seen with canagliflozin 100 and 300 mg versus placebo after 2 years (-1.7%, 
      -2.1%, -0.8%; differences of -0.9% and -1.2%), but not at other skeletal sites 
      (normal age-related bone loss, ~0.5-1.0%/year). Changes in beta-CTX and total hip 
      BMD were significantly associated with weight loss, which is known to increase 
      bone resorption markers and decrease BMD. Canagliflozin was associated with a 
      higher fracture incidence in an interim analysis of the CANagliflozin 
      cardioVascular Assessment Study (CANVAS) in patients with a history or high risk 
      of cardiovascular disease (incidence per 100 patient-years of 1.6, 1.6, and 1.1 
      with canagliflozin 100 and 300 mg and placebo), but not in other clinical studies 
      of patients with T2DM. Fractures tended to occur as early as 12 weeks after 
      initiating treatment and were primarily located in the distal parts of the upper 
      and lower extremities. The reason for increased fracture risk with canagliflozin 
      treatment is unknown, but is likely not related to a direct effect of 
      canagliflozin on bone-related biomarkers. Data from ongoing canagliflozin 
      studies, including CANVAS, will provide additional information on fracture risk 
      in patients with T2DM.
FAU - Blevins, Thomas C
AU  - Blevins TC
AD  - a Texas Diabetes and Endocrinology , Austin , TX , USA.
FAU - Farooki, Azeez
AU  - Farooki A
AD  - b Memorial Sloan Kettering Cancer Center , New York , NY , USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20161128
PL  - England
TA  - Postgrad Med
JT  - Postgraduate medicine
JID - 0401147
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Biomarkers/blood
MH  - Blood Glucose/drug effects
MH  - Bone Density/*drug effects
MH  - Canagliflozin/*adverse effects/*therapeutic use
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/therapeutic use
MH  - Male
MH  - Osteoporosis/drug therapy/*etiology
MH  - Sodium-Glucose Transporter 2/*adverse effects/*therapeutic use
OTO - NOTNLM
OT  - Bone mineral density
OT  - bone mineral metabolism
OT  - bone turnover markers
OT  - canagliflozin
OT  - fractures
OT  - type 2 diabetes mellitus
EDAT- 2016/11/30 06:00
MHDA- 2017/02/07 06:00
CRDT- 2016/11/30 06:00
PHST- 2016/11/30 06:00 [pubmed]
PHST- 2017/02/07 06:00 [medline]
PHST- 2016/11/30 06:00 [entrez]
AID - 10.1080/00325481.2017.1256747 [doi]
PST - ppublish
SO  - Postgrad Med. 2017 Jan;129(1):159-168. doi: 10.1080/00325481.2017.1256747. Epub 
      2016 Nov 28.