title: Model analysis of effect of canagliflozin (Invokana), a sodium-glucose cotransporter 2 inhibitor, to alter plasma 1,5-anhydroglucitol.
abstract: BACKGROUND
  Renal reabsorption of 1,5-anhydroglucitol (AG) is competitively inhibited by elevated glucose and leads to depleted plasma AG in diabetes. Plasma AG recovery in diabetes normally correlates with improved glycemic control. However, use of sodium-glucose co-transporter 2 (SGLT2) inhibitors (e.g., canagliflozin) to treat diabetes by inhibition of renal glucose reabsorption can negate this correlation, via an indirect effect (increase of renal filtrate glucose concentration) to inhibit AG reabsorption by sodium-glucose co-transporter 4 (SGLT4). Conversely, then, AG measurement might be useful as an independent marker for SGLT2 inhibitor activity.
  
  
  METHODS
  Using an AG mass balance model, we analyzed literature data on plasma AG before and after initiation of canagliflozin therapy (CT) to quantitatively characterize the effect of CT on AG reabsorption.
  
  
  RESULTS
  According to model calculations, modest decreases (<5%) in fractional reabsorption of AG account for the drastic decrease in [AG] observed during CT. Decreases are predicted to be rapid (t1/2<3days) after CT initiation.
  
  
  CONCLUSIONS
  CT negates the usual premise of AG measurement (that [AG] should increase with improved glycemic control). However, according to model calculations, a substantial and likely rapid effect of CT on [AG] means that AG measurement might provide an early marker for CT activity.
authors.affiliation: Jefferson University Hospitals, Philadelphia, PA 19107, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Fortuna
authors.affiliation: Jefferson University Hospitals, Philadelphia, PA 19107, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: McCloskey
authors.affiliation: Jefferson University Hospitals, Philadelphia, PA 19107, USA. Electronic address: douglas.stickle@jefferson.edu.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Stickle
mesh_terms: D000068896:Canagliflozin / Q000494:pharmacology*; D003847:Deoxyglucose / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008954:Models, Biological; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C006584:1,5-anhydroglucitol; D003847:Deoxyglucose
keywords: Anhydroglucitol; Canagliflozin; Diabetes; Invokana; Mathematical model; SGLT2 inhibitors