A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment.
OBJECTIVE
To determine whether dapagliflozin, which selectively inhibits renal glucose reabsorption, lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents (OADs).


METHODS
This was a randomized, double-blind, three-arm parallel-group, placebo-controlled, 26-center trial (U.S. and Canada). Based on data from an insulin dose-adjustment setting cohort (n = 4), patients in the treatment cohort (n = 71) were randomly assigned 1:1:1 to placebo, 10 mg dapagliflozin, or 20 mg dapagliflozin, plus OAD(s) and 50% of their daily insulin dose. The primary outcome was change from baseline in A1C at week 12 (dapagliflozin vs. placebo, last observation carried forward [LOCF]).


RESULTS
At week 12 (LOCF), the 10- and 20-mg dapagliflozin groups demonstrated -0.70 and -0.78% mean differences in A1C change from baseline versus placebo. In both dapagliflozin groups, 65.2% of patients achieved a decrease from baseline in A1C > or =0.5% versus 15.8% in the placebo group. Mean changes from baseline in fasting plasma glucose (FPG) were +17.8, +2.4, and -9.6 mg/dl (placebo, 10 mg dapagliflozin, and 20 mg dapagliflozin, respectively). Postprandial glucose (PPG) reductions with dapagliflozin also showed dose dependence. Mean changes in total body weight were -1.9, -4.5, and -4.3 kg (placebo, 10 mg dapagliflozin, and 20 mg dapagliflozin). Overall, adverse events were balanced across all groups, although more genital infections occurred in the 20-mg dapagliflozin group than in the placebo group.


CONCLUSIONS
In patients receiving high insulin doses plus insulin sensitizers who had their baseline insulin reduced by 50%, dapagliflozin decreased A1C, produced better FPG and PPG levels, and lowered weight more than placebo.
Wilding
John P H
JP
University of Liverpool, School of Clinical Sciences, Liverpool, England. j.p.h.wilding@liv.ac.uk
Norwood
Paul
P
T'joen
Caroline
C
Bastien
Arnaud
A
List
James F
JF
Fiedorek
Fred T
FT
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; C529054:dapagliflozin