title: Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.
  
  
  METHODS
  In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from baseline in A1C at 52 weeks. Secondary end points included change in fasting plasma glucose (FPG) and systolic blood pressure (BP), and percent change in body weight, triglycerides, and HDL cholesterol. Safety was assessed based on adverse event (AE) reports.
  
  
  RESULTS
  At 52 weeks, canagliflozin 300 mg demonstrated noninferiority and, in a subsequent assessment, showed superiority to sitagliptin 100 mg in reducing A1C (-1.03% [-11.3 mmol/mol] and -0.66% [-7.2 mmol/mol], respectively; least squares mean difference between groups, -0.37% [95% CI, -0.50 to -0.25] or -4.0 mmol/mol [-5.5 to -2.7]). Greater reductions in FPG, body weight, and systolic BP were observed with canagliflozin versus sitagliptin (P < 0.001). Overall AE rates were similar with canagliflozin (76.7%) and sitagliptin (77.5%); incidence of serious AEs and AE-related discontinuations was low for both groups. Higher incidences of genital mycotic infections and osmotic diuresis-related AEs were observed with canagliflozin, which led to one discontinuation. Hypoglycemia rates were similar in both groups.
  
  
  CONCLUSIONS
  Findings suggest that canagliflozin may be a new therapeutic tool providing better improvement in glycemic control and body weight reduction than sitagliptin, but with increased genital infections in subjects with type 2 diabetes using metformin plus sulfonylurea.
authors.affiliation: Rudolfstiftung Hospital-Vienna, Vienna, Austria. guntram.schernthaner@wienkav.at
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.forename: Michael
authors.initials: M
authors.lastname: Guarisco
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Yee
authors.forename: Masato
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: William
authors.initials: W
authors.lastname: Canovatchel
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D013876:Thiophenes; D014230:Triazoles
references.citation: J Clin Invest. 1987 May;79(5):1510-5
references.pmid: 3571496
references.citation: Diabetes Obes Metab. 2013 Apr;15(4):372-82
references.pmid: 23279307
references.citation: Diabetes Care. 2005 May;28(5):1083-91
references.pmid: 15855571
references.citation: Ann Intern Med. 2012 Mar 20;156(6):405-15
references.pmid: 22431673
references.citation: Diabetologia. 2009 Oct;52(10):2046-55
references.pmid: 19688338
references.citation: Diabetes Obes Metab. 2007 Mar;9(2):194-205
references.pmid: 17300595
references.citation: Kidney Int. 2009 Jun;75(12):1272-1277
references.pmid: 19357717
references.citation: Diabetes Obes Metab. 2011 Oct;13(10):928-38
references.pmid: 21672123
references.citation: Diabetes Care. 2012 Jun;35(6):1232-8
references.pmid: 22492586
references.citation: Diabetes Obes Metab. 2011 Jul;13(7):669-72
references.pmid: 21457428
references.citation: Diabetes. 2011 Mar;60(3):890-8
references.pmid: 21357472
references.citation: Diabetes Care. 2006 Sep;29(9):2137-9
references.pmid: 16936168
references.citation: Diabetes Obes Metab. 2012 Jun;14(6):539-45
references.pmid: 22226086
references.citation: Diabetes Care. 2012 Jun;35(6):1364-79
references.pmid: 22517736
references.citation: J Clin Invest. 2012 Dec;122(12):4667-74
references.pmid: 23187122
references.citation: J Med Chem. 2010 Sep 9;53(17):6355-60
references.pmid: 20690635
references.citation: Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
references.pmid: 22187469
references.citation: Diabetes Care. 2005 May;28(5):995-1000
references.pmid: 15855556
references.citation: Diabetes Care. 2004 Nov;27(11):2628-35
references.pmid: 15504997
references.citation: Diabetes Obes Metab. 2010 Nov;12(11):1004-12
references.pmid: 20880347
references.citation: PLoS One. 2012;7(2):e30555
references.pmid: 22355316
references.citation: Diabetes Obes Metab. 2007 Sep;9(5):733-45
references.pmid: 17593236
references.citation: Horm Metab Res. 2002 Apr;34(4):217-21
references.pmid: 11987033
references.citation: Drugs. 2010 Mar 5;70(4):377-85
references.pmid: 20205482
references.citation: Diabetologia. 2011 Dec;54(12):3047-54
references.pmid: 21959959
references.citation: Ann Intern Med. 2011 May 17;154(10):672-9
references.pmid: 21576535
references.citation: Eur J Pharmacol. 2009 Sep 15;618(1-3):98-104
references.pmid: 19615995
references.citation: J Diabetes Complications. 2012 Sep-Oct;26(5):442-9
references.pmid: 22673566
references.citation: Adv Exp Med Biol. 2010;654:515-35
references.pmid: 20217513
references.citation: Diabet Med. 2007 Apr;24(4):350-8
references.pmid: 17335466