Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin
Diabetes, Obesity and Metabolism, 05/02/2012
Devineni D et al. – In subjects receiving insulin and oral antihyperglycaemic therapy, canagliflozin was well tolerated without evidence for glucose malabsorption, had pharmacokinetic characteristics consistent with once–daily dosing, and improved glycaemic control.Methods
- This was a randomized, double-blind, placebo-controlled, parallel-group, 28-day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent.
- Subjects were treated with canagliflozin 100 mg QD or 300 mg twice daily (BID) or placebo.
- Safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of canagliflozin were examined.
- Glucose malabsorption following a 75-g oral glucose challenge was also examined.
- Canagliflozin pharmacokinetics were dose-dependent, and the elimination half-life ranged from 12 to 15 h.
- After 28 days, the renal threshold for glucose excretion was reduced; urinary glucose excretion was increased; and A1C, fasting plasma glucose and body weight decreased in subjects administered canagliflozin (A1C reductions: 0.19% with placebo, 0.73% with 100 mg QD, 0.92% with 300 mg BID; body weight changes: 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg QD, 1.19 kg reduction with 300 mg BID).
- Glucose malabsorption was not observed with canagliflozin treatment.
- There were no deaths, serious adverse events or severe hypoglycaemic episodes.
- The incidence of adverse events was similar across groups.
- There were no clinically meaningful changes in routine laboratory safety tests, vital signs or electrocardiograms.