Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial.
OBJECTIVE
Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose cotransporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes.


METHODS
This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with A1C 7.0-10% (n = 485) were randomly assigned to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin once daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1-12% (high-A1C exploratory cohort; n = 73) were randomly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin. The primary end point was change from baseline in A1C in the main cohort, statistically tested using an ANCOVA.


RESULTS
In the main cohort, mean A1C changes from baseline at week 24 were -0.23% with placebo and -0.58, -0.77 (P = 0.0005 vs. placebo), and -0.89% (P < 0.0001 vs. placebo) with 2.5, 5, and 10 mg dapagliflozin, respectively. Signs, symptoms, and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results.


CONCLUSIONS
Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes.
Ferrannini
Ele
E
Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy. ferranni@ifc.cnr.it
Ramos
Silvia Jimenez
SJ
Salsali
Afshin
A
Tang
Weihua
W
List
James F
JF
D001559:Benzhydryl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy*; D004035:Diet Therapy; D004311:Double-Blind Method; D005081:Exercise Therapy; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D010919:Placebos; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010919:Placebos; C529054:dapagliflozin