Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin.
OBJECTIVE
Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is being investigated for the treatment of type 2 diabetes mellitus (T2DM).


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.


RESULTS
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.


CONCLUSIONS
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.
Janssen Research & Development, LLC, Raritan, NJ 08869, USA. DDevinen@its.jnj.com
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D
Devineni
L
L
Morrow
M
M
Hompesch
D
D
Skee
A
A
Vandebosch
J
J
Murphy
K
K
Ways
S
S
Schwartz
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000068896:Canagliflozin; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D013876:Thiophenes; D000068896:Canagliflozin