recommended starting dose of Canagliflozin is 100 mg once daily, taken before
the first meal of the day. In patients tolerating Canagliflozin 100 mg once
daily who have an eGFR of 60 mL/min/1.73
m2 or greater and require additional glycemic
A novel thiophene derivate with a C glycoside bearing a hetero-aromatic
ring formed a metabolically more stable, highly potent and selective inhibitors
for sodium glucose co-transporter 2 than O glycoside (Nomura et al., 2010).
the US Food and Drug Administration (US FDA) in 2013 (Vlotides & Mertens, 2014).
class: Sodium glucose co-transporter 2 inhibitors SGL-2 inhibitors.
Further, SGLT2 inhibitors may be associated
with increased risk for lower limbs amputations; theoretically, these agents
increase the excretion of serum glucose to the urine thus lowering its osmotic
pressure, enhancing the osmotic diuresis and lowering the intravascular volume.
To date this effect is under investigation and no clear evidence was made(Yuan et al., 2017)
SGLT2 inhibitors may increase the risk of bone
fractures; in patients with T2DM, canagliflozin
showed significant reductions in total hip Bone Marrow Density and increases in
bone formation and resorption biomarkers(Bilezikian et al., 2016). Recent data indicate that SGLT2 inhibitors may alter calcium
and phosphate homeostasis (secondary hyperparathyroidism induced by increased
phosphate reabsorption) and thereby potentially affect bone mass and fracture
SGLT2 inhibitors are associated with an
increased risk of euglycemic ketoacidosis (Taylor, Blau, & Rother, 2015) Reviews of DKA in people taking SGLT2
inhibitors revealed that a significant proportion of cases occurred in people
with type 1diabetes for whom SGLT2
inhibitors are not licensed. Other situations that predisposed to DKA in people
with type 2 diabetes were those of relative insulin deficiency, including acute
illness, surgery, alcohol abuse and people with an underlying low reserve of
insulin. Even if most reported episodes of SGLT2 inhibitor-associated
ketoacidosis occurred in patients with type 1 diabetes, rare events were also
observed in patients with T2DM (Morris, 2017)
Glycosuria induces an osmotic diuresis that
may result in increased urination in people taking SGLT2 inhibitors. Associated
with this is a slightly raised incidence of side effects related to volume
depletion, dehydration and postural hypotension for this reason these
medication are contraindicated when glomerular filtration rate less than 30
ml/min/1.73 m2. Acute kidney injury can occur, particularly if eGFR
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