Canagliflozin: a novel treatment option for type 2 diabetes

Figures & data

Table 1 Efficacy of canagliflozin in clinical trials

Study	Design and intervention	Primary outcome	Secondary outcomes
Stenlöf et al^Citation12	– 26 week R, DB, PC, PG – Main study: can 100 mg (n=195), can 300 mg (n=197), or pcb (n=192) added to diet and exercise – High glycemic: can 100 mg (n=47) or can 300 mg (n=44) added to diet and exercise	– Reduction in A1c from baseline – Main study (LS mean difference compared to pcb): can 100 mg: −0.91%; can 300 mg: −1.16% – High glycemic: can 100 mg: −2.13%; can 300 mg: −2.56%	FBG: reduced by 27 mg/dL with can 100 mg and 34 mg/dL with can 300 mg BW: −1.9 kg with can 100 mg and −2.9 kg with can 300 mg (LS mean difference versus pcb)
Rosenstock et al^Citation13	– 26 week R, DB, PC, PG, DR study – Can 100 mg (n=64), can 300 mg (n=64), sita 100 mg (n=65), or pcb (n=65) added to baseline metformin therapy	– Reduction in A1c from baseline – Can 100 mg: −0.76%; can 300 mg: −0.92%; sita 100 mg: −0.74%; pcb: −0.22%	FBG: can 100 mg: −25.2 mg/dL; can 300 mg: −25.2 mg/dL; sita 100 mg: −12.6 mg/dL; pcb: 3.6 mg/dL BW: can 100 mg: −2.6 kg; can 300 mg: −3.4 kg; sita 100 kg: −0.4 kg; pcb: −0.8 kg
Schernthaner et al^Citation14	– 52 week R, DB, AC, NI – Can 300 mg (n=378), Sita 100 mg (n=378) with metformin plus sulfonylurea	– Reduction in A1c from baseline – Can 300 mg: −1.03%; Sita 100 mg: −0.66%	FBG: can 300 mg: −28.7 mg/dL; Sita 100 mg: −2.2 mg/dL BW: can 300 mg: −2.6 kg; sita 100 mg: −0.1 kg
Devineni et al^Citation15	– 28 day R, DB, PC – Can 100 mg (n=10), can 600 mg (n=10), or pcb (n=9) with insulin therapy	– Reduction in A1c from baseline – Can 100 mg: −0.37%;^ can 600 mg: −0.55%^	FBG: can 100 mg: −2.37 mmol/L;^ can 600 mg: −2.48 mmol/L^ BW: can 100 mg: −0.68 kg;^ can 600 mg: −1.24 kg^
Yale et al^Citation16	– 26 week R, DB, PC study in patients with stage 3 CKD – Can 100 mg (n=90), can 300 mg (n=89), or pcb (n=90) in addition to background therapy	– Reduction in A1c from baseline – Can 100: −0.37%; can 300 mg: −0.44%; pcb: −0.03%	FBG: not statistically different between groups BW: can 100: −1.4 kg; can 300 mg: −1.6 kg; pcb: 0.2 kg
Bode et al^Citation17	– 26 week R, DB, PC study in patients aged 55–80 years – Can 100 mg, can 300 mg, or pcb in addition to background therapy	– Reduction in A1c from baseline – Can 100: −0.60%; can 300 mg: −0.73%; pcb: −0.03%	FBG: can 100 mg: −25.5 mg/dL; can 300 mg: 27.7 mg/dL BW: can 100 mg: −2.1 kg; can 300 mg: −2.7 kg

Note:

^ Compared to placebo.

Abbreviations: AC, active control; A_1c, hemoglobin A_1c; BW, body weight; Can/can, canagliflozin; CKD, chronic kidney disease; DB, double-blind; DR, dose ranging; FBG, fasting blood glucose; LS, least squares, NI, noninferiority; PC, placebo-controlled; pcb, placebo; PG, parallel group; R, randomized; Sita/sita, sitagliptin.

Table 2 Safety in specific populations

Study	Design and intervention	Primary outcome	Adverse drug events
Yale et al^Citation16	– 26 week R, DB, PC – stage 3 chronic kidney disease (CKD) (eGFR ≥30 and <50 mL/min/1.73 m^2) – can 100 mg (n=90), can 300 mg (n=89), or pcb (n=90)	– Reduction in A1c from baseline – LS mean difference compared to pcb: can 100 mg: 0.3% (P<0.05); can 300 mg: 0.4% (P<0.001)	– Mycotic infections: can 100 mg (n=2); can 300 mg (n=2); pcb (n=0) – Change in eGFR: can 100 mg: −9.1%; can 300 mg: −10.1%; pcb; −4.5% – Change in BUN: can 100 mg: +12.1%; can 300 mg: +12.5%; pcb: +4.9%
Bode et al^Citation17	– 26 week R, DB, PC – Average age of 63.6 years – Can 100 mg (n=241), can 300 mg (n=236), or pcb (n=237)	– Reduction in A1c from baseline – Compared to pcb: Can 100 mg: −0.57%; can 300 mg: −0.7%	– Mycotic infections: can 100 mg (n=22); can 300 mg (n=20); pcb (n=2) – Pollakiuria: can 100 mg (n=6); can 300 mg (n=12); pcb (n=5) – Polyuria: can 100 mg (n=4); can 300 mg (n=4); pcb (n=0) – Hypoglycemia mono-therapy: can 100 mg (n=4); can 300 mg (n=3); pcb (n=2) – Hypoglycemia combination therapy: can 100 mg (n=78); can 300 mg (n=82); pcb (n=66)

Abbreviations: R, randomized; DB, double-blind; PC, placebo-controlled; eGFR, estimated glomerular filtration rate; can, canagliflozin; pcb, placebo; A_1c, hemoglobin A_1c; LS, least squares; BUN, blood urea nitrogen.

Table 3 Adverse reactions

Study	Female mycotic infection, n (%)	Male mycotic infection, n (%)	Urinary tract infection, n (%)	Pollakuria, n (%)	Polyuria, n (%)	Hypoglycemia, n (%)
Stenlöf et al^Citation12 (2013)	Pcb: 4 (3.8)	Pcb: 0	Pcb: 8 (4.2)	Pcb: 1 (0.5)	Pcb: 0	Pcb: 5 (2.6)
	C100: 10 (8.8)	C100: 2 (2.5)	C100: 14 (7.2)	C100: 5 (2.6)	C100: 0	C100: 7 (3.6)
	C300: 8 (7.4)	C300: 5 (5.6)	C300: 10 (5.1)	C300: 6 (3)	C300: 6 (3)	C300: 6 (3)
Rosenstock et al^Citation13 (2012)	Pcb: 0	Pcb: NR	Pcb: 4 (6)	Pcb: < 2%	NR	Pcb: 1 (2)
	C100: 2 (3)	C100: NR	C100: 2 (3)	C100: < 5%		C100: 1 (2)
	C300: 1 (2)	C300: NR	C300: 2 (3)	C300: < 5%		C300: 0
Schernthaner et al^Citation14 (2013)	Sit100: 7 (4.3)	Sit100: 1 (0.5)	Sit100: 21 (5.6)	Sit100: 5 (1.3)	Sit100: 0	Sit100: 40.7%
	C300: 26 (15.3)	C300: 19 (9.2)	C300: 15 (4.0)	C300: 6 (1.6)	C300:3 (0.8)	C300: 43.2%
Devineni et al^Citation15 (2012)	NR	NR	NR	NR	NR	Pcb: 3 (33) C100: 6 (60) C300: 3 (30)
Yale et al^Citation16 (2013)	Pcb: 0	Pcb: 0	Pcb: 5 (5.6)	Pcb: 1 (1.1)	Pcb: 0	Pcb: 36.4%^
	C100: 1 (3.1)	C100: 1 (1.7)	C100: 5 (5.6)	C100: 2 (2.2)	C100:0	C100: 52.9%^
	C300: 1 (2.4)	C300: 1 (2.1)	C300: 7 (7.9)	C300: 4 (4.5)	C300: 0	C300: 51.2%^
Bode et al^Citation17 (2013)	Pcb: 2 (2.1)	Pcb: 0	Pcb: 12 (5.1)	Pcb: 5 (2.1)	Pcb: 0	Pcb: 33.7%^
	C100: 18 (15.4)	C100: 4 (3.2)	C100: 14 (5.8)	C100: 6 (2.5)	C100: 4 (1.7)	C100: 43.1%^
	C300: 12 (11.2)	C300: 8 (6.2)	C300: 19 (8.1)	C300: 12 (5.1)	C300: 4 (1.7)	C300: 47.4%^

Note:

^ Those treated with other hypoglycemic therapy.

Abbreviations: Pcb, placebo; C100, canagliflozin 100 mg; C300, canagliflozin 300 mg; NR, not reported; Sit100, sitagliptin 100 mg.

Stenlöf K Cefalu WT Kim KA Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise Diabetes Obes Metab 2013 15 4 372 382 23279307

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Rosenstock J Aggarwal N Polidori D Canagliflozin DIA 2001 Study Group Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes Diabetes Care 2012 35 6 1232 1238 22492586

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Schernthaner G Gross JL Rosenstock J Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea Diabetes Care 2013 36 9 2508 2515 23564919

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Devineni D Morrow L Hompesch M Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin Diabetes Obes Metab 2012 14 6 539 545 22226086

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Yale JF Bakris G Cariou B Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease Diabetes Obes Metab 2013 15 5 463 473 23464594

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Bode B Stenlöf K Sullivan D Fung A Usiskin K Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial Hosp Pract 2013 41 2 72 84

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