Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study.
OBJECTIVE
Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for treatment of type 2 diabetes mellitus (T2DM). The long-term efficacy and safety of canagliflozin monotherapy were evaluated over 52 weeks in patients with T2DM inadequately controlled with diet and exercise.


METHODS
This randomized, double-blind, Phase 3 study included a placebo-controlled, 26-week core period (canagliflozin 100 or 300 mg vs placebo) and an active-controlled, 26-week extension (blinded switch of placebo-treated patients to sitagliptin 100 mg [placebo/sitagliptin]).


BACKGROUND
ClinicalTrials.gov, NCT01081834.


METHODS
Efficacy endpoints assessed at 52 weeks included changes in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and systolic blood pressure (BP); and percentage changes in body weight and fasting plasma lipids. Adverse events (AEs) were recorded throughout the study. Efficacy data are reported for canagliflozin 100 and 300 mg (placebo/sitagliptin group was used to maintain the double-blind and to serve as a control group for safety purposes; not as an efficacy comparator); safety data are reported for canagliflozin 100 and 300 mg and placebo/sitagliptin.


RESULTS
Efficacy analyses included 451 patients who were randomized and dosed, entered the extension, and did not receive rescue therapy during the core period. Safety analyses included 584 patients who were randomized and dosed. At Week 52, canagliflozin 100 and 300 mg provided dose-related decreases from baseline in HbA1c of -0.81% and -1.11%. Canagliflozin 100 and 300 mg decreased FPG (-1.5 and -2.2 mmol/L [-27.4 and -39.1 mg/dL]), body weight (-3.3% and -4.4%), and systolic BP (-1.4 and -3.9 mmHg); decreased triglycerides and increased HDL-C and LDL-C were also seen. Over 52 weeks, overall AE rates were 67.2%, 66.0%, and 64.1% with canagliflozin 100 and 300 mg and placebo/sitagliptin; rates of serious AEs and AE-related discontinuations were low across groups. Compared with placebo/sitagliptin, canagliflozin was associated with higher rates of genital mycotic infections and AEs related to osmotic diuresis; these led to few discontinuations. Rates of volume depletion AEs and documented hypoglycemia were low across groups.


CONCLUSIONS
Canagliflozin monotherapy provided sustained improvement in glycemic control and body weight reduction, and was generally well tolerated in patients with T2DM over 52 weeks.
Clinical Trial Center, Sahlgrenska University Hospital , Gothenburg , Sweden.
Kaj
K
Stenlöf
William T
WT
Cefalu
Kyoung-Ah
KA
Kim
Esteban
E
Jodar
Maria
M
Alba
Robert
R
Edwards
Cindy
C
Tong
William
W
Canovatchel
Gary
G
Meininger
D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000068896:Canagliflozin; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004032:Diet; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D000068896:Canagliflozin; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010919:Placebos; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D014230:Triazoles; D014280:Triglycerides