title: Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects.
abstract: Canagliflozin, a potent, selective sodium glucose co-transporter 2 inhibitor in development for treatment of type 2 diabetes, lowers plasma glucose (PG) by lowering the renal threshold for glucose (RT(G) ) and increasing urinary glucose excretion (UGE). An ascending single oral-dose phase 1 study investigated safety, tolerability and pharmacodynamics of canagliflozin in healthy men (N = 63) randomized to receive canagliflozin (n = 48) or placebo (n = 15). Canagliflozin (10, 30, 100, 200, 400, 600 or 800 mg q.d. or 400 mg b.i.d.) was administered to eight cohorts (six subjects/cohort: canagliflozin; two subjects/cohort: placebo). Dose dependently, canagliflozin decreased calculated 24-h mean RT(G) with maximal reduction to approximately 60 mg/dl, and increased mean 24-h UGE. At doses >200 mg administered before breakfast, canagliflozin reduced postprandial PG and serum insulin excursions at that meal. Canagliflozin was generally well tolerated; most adverse events were mild and no hypoglycaemia was reported. These results support further study of canagliflozin.
authors: Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ 08869, USA. ssha@its.jnj.com
authors: S
authors: S
authors: Sha
authors: D
authors: D
authors: Devineni
authors: A
authors: A
authors: Ghosh
authors: D
authors: D
authors: Polidori
authors: S
authors: S
authors: Chien
authors: D
authors: D
authors: Wexler
authors: K
authors: K
authors: Shalayda
authors: K
authors: K
authors: Demarest
authors: P
authors: P
authors: Rothenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006029:Glycosuria / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin