Efficacy and Safety of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes.
OBJECTIVE
This study assessed the efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in adults with type 1 diabetes.


METHODS
This 18-week, double-blind, phase 2 study randomized 351 patients (HbA1c 7.0-9.0% [53-75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion to canagliflozin 100 or 300 mg or placebo. The primary end point was the proportion of patients achieving at week 18 both HbA1c reduction from baseline of ≥0.4% (≥4.4 mmol/mol) and no increase in body weight. Other end points included changes in HbA1c, body weight, and insulin dose, as well as hypoglycemia incidence. Safety was assessed by adverse event (AE) reports.


RESULTS
More patients had both HbA1c reduction ≥0.4% and no increase in body weight with canagliflozin 100 and 300 mg versus placebo at week 18 (36.9%, 41.4%, 14.5%, respectively; P < 0.001). Both canagliflozin doses provided reductions in HbA1c, body weight, and insulin dose versus placebo over 18 weeks. The incidence of hypoglycemia was similar across groups; severe hypoglycemia rates were low (1.7-6.8%). Overall incidence of AEs was 55.6%, 67.5%, and 54.7% with canagliflozin 100 and 300 mg and placebo; discontinuation rates were low (0.9-1.3%). Increased incidence of ketone-related AEs (5.1%, 9.4%, 0%), including the specific AE of diabetic ketoacidosis (DKA) (4.3%, 6.0%, 0%), was seen with canagliflozin 100 and 300 mg versus placebo.


CONCLUSIONS
Canagliflozin provided reductions in HbA1c, body weight, and insulin dose with no increase in hypoglycemia, but increased rates of ketone-related AEs, including DKA, in adults with type 1 diabetes inadequately controlled with insulin.
Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA University of California, San Diego, La Jolla, CA rrhenry@outlook.com.
Robert R
RR
Henry
Janssen Research & Development, LLC, Raritan, NJ.
Payal
P
Thakkar
Janssen Research & Development, LLC, Raritan, NJ.
Cindy
C
Tong
Janssen Research & Development, LLC, San Diego, CA.
David
D
Polidori
Janssen Research & Development, LLC, Raritan, NJ.
Maria
M
Alba
D000328:Adult; D000068896:Canagliflozin / Q000008:administration & dosage / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D007328:Insulin; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin