Connect with us

Products

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

INVOKANA® (canagliflozin)

Medical Information

Prescribing Information Comparison of INVOKANA to Other SGLT2 Inhibitors

Last Updated: 09/14/2026

Summary

There are no phase 3 clinical studies that directly compare the safety and efficacy of INVOKANA to other sodium-glucose cotransporter-2 (SGLT2) inhibitors, including dapagliflozin, empagliflozin, and ertugliflozin. An indirect comparison between INVOKANA and other SGLT2 inhibitors cannot be made due to differences in patient populations, study designs, and procedures.
Summary information on each product is provided (see Table: Summary of INVOKANA, Dapagliflozin, Empagliflozin, and Ertugliflozin). The summary table does not imply head-to-head comparison. Please refer to each product’s Full Prescribing Information for complete information.
A phase 1, randomized, double-blind, crossover study in healthy subjects (N=54) compared the pharmacodynamic effects of canagliflozin 300 mg and dapagliflozin 10 mg on urinary glucose excretion (UGE), renal threshold for glucose (RT_G), and postprandial glucose (PPG). Canagliflozin 300 mg was associated with a greater increase in UGE, a greater reduction in RT_G, and smaller excursions in PPG compared with dapagliflozin 10 mg.¹

Summary of INVOKANA², Dapagliflozin³, Empagliflozin⁴, and Ertugliflozin⁵

	INVOKANA²	Dapagliflozin³	Empagliflozin⁴	Ertugliflozin⁵
Boxed Warning	-	-	-	-
Indications and Usage	Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ≥10 years with T2DM To reduce the risk of MACE in adults with T2DM and established CVD To reduce the risk of ESKD, doubling of serum creatinine, CV death, and HHF in adults with T2DM and diabetic nephropathy with albuminuria >300 mg/day	Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ≥10 years with T2DM To reduce the risk of HHF in adults with T2DM and established CVD or multiple CV risk factors To reduce the risk of CV death, HHF, and urgent heart failure in adults with heart failure To reduce the risk of sustained eGFR decline, ESKD, CV death, and HHF in adults with CKD at risk of progression	Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged ≥10 years with T2DM To reduce the risk of CV death in adult patients with T2DM and established CVD To reduce the risk of CV death and HHF in adults with heart failure To reduce the risk of sustained eGFR decline, ESKD, CV death, and hospitalization in adults with CKD at risk of progression	Adjunct to diet and exercise to improve glycemic control in adults with T2DM
Limitation of Use	INVOKANA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus INVOKANA is not recommended for use to improve glycemic control in adults with T2DM with an eGFR <30 mL/min/1.73 m²	Dapagliflozin is not recommended in patients with T1DM. Dapagliflozin is not recommended for use to improve glycemic control in adults with T2DM with eGFR <45 mL/min/1.73 m² Dapagliflozin is not recommended for the treatment of CKD in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease	EMPA is not recommended for use to improve glycemic control in patients with T1DM. It may increase the risk of DKA in these patients EMPA is not recommended for use to improve glycemic control in adults with T2DM with an eGFR <30 mL/min/1.73 m² EMPA is not recommended for the treatment of CKD in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease	Ertugliflozin is not recommended for use to improve glycemic control in patients with T1DM.
Recommended Starting Dose	Dosage for glycemic control in adults and pediatric patients aged ≥10 years INVOKANA 100 mg once daily, taken before the first meal of the day (see also Food Effects & PK/PD) For additional glycemic control, the dosage of INVOKANA may be increased to the maximum recommended dosage of 300 mg once daily Dosage for other indications in adults INVOKANA 100 mg once daily to reduce the risk of MACE in adults with T2DM and established CVD INVOKANA 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and HHF in adults with T2DM and diabetic nephropathy with albuminuria >300 mg/day	Dapagliflozin 5 mg once daily, taken in the morning, with or without food (see also Food Effects & PK/PD) For additional glycemic control, the dosage can be increased to 10 mg orally once daily Dapagliflozin 10 mg once daily in adults: to reduce the risk of sustained eGFR decline, ESKD, CV death, and HHF in adults with CKD at risk of progression to reduce the risk of CV death, HHF, and urgent heart failure in adults with heart failure to reduce the risk of HHF in adults with T2DM and established CVD or multiple CV risk factors	EMPA 10 mg once daily in the morning, taken with or without food (see also Food Effects & PK/PD) For pediatric patients aged ≥10 years with T2DM: EMPA 10 mg once daily in the morning, taken with or without food For additional glycemic control, dose may be increased to 25 mg orally once daily in patients tolerating 10 mg once daily	Ertugliflozin 5 mg once daily, taken in the morning with or without food (see also Food Effects & PK/PD) For additional glycemic control, the dosage may be increased to 15 mg orally once daily in patients tolerating ertugliflozin
Dose Adjustments	Increase to 200 mg once daily, with maximum dose of 300 mg once daily if tolerating 100 mg once daily, have an eGFR of ≥60 mL/min/1.73 m² Increase to 200 mg once daily if tolerating 100 mg once daily, have an eGFR of <60 mL/min/1.73 m² Withhold INVOKANA at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume INVOKANA when the patient is clinically stable and has resumed oral intake	Increase to 10 mg once daily if tolerating 5 mg once daily and require additional glycemic control If the eGFR falls below 25 mL/min/1.73 m² while receiving treatment with dapagliflozin, patients may continue dapagliflozin 10 mg orally once daily to reduce the risk of eGFR decline, ESKD, CV death, and HHF Withhold dapagliflozin for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume dapagliflozin when the patient is clinically stable and has resumed oral intake	In patients tolerating, the dose may be increased to 25 mg for additional glycemic control Withhold EMPA for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume EMPA when the patient is clinically stable and has resumed oral intake	Increase to 15 mg once daily if tolerating 5 mg once daily and needing additional glycemic control Withhold ertugliflozin for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume ertugliflozin when the patient is clinically stable and has resumed oral intake
Moderate Renal Impairment	INVOKANA is limited to 100 mg once daily at eGFR 30 to <60 mL/min/1.73 m² INVOKANA initiation is not recommended for patients with eGFR <30 mL/min/1.73 m² Adult patients taking INVOKANA with albuminuria >300 mg/day may continue INVOKANA 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and HHF	Not recommended for use to improve glycemic control in adults with T2DM with an eGFR <45 mL/min/1.73 m² If the eGFR falls below 25 mL/min/1.73 m² while receiving treatment with dapagliflozin, patients may continue dapagliflozin 10 mg orally once daily to reduce the risk of eGFR decline, ESKD, CV death, and HHF	EMPA should not be initiated for glycemic control in patients with an eGFR <30 mL/min/1.73 m²	Ertugliflozin is not recommended for use in patients with an eGFR <45 mL/min/1.73 m²
eGFR limits	INVOKANA is limited to 100 mg once daily at eGFR 30 to <60 mL/min/1.73 m² INVOKANA should not be initiated at eGFR <30 mL/min/1.73 m²; however, patients with albuminuria >300 mg/day may continue 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and HHF	Not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR <45 mL/min/1.73 m² Initiation of dapagliflozin is not recommended in patients with an eGFR <25 mL/min/1.73 m²; however, patients may continue 10 mg once daily to reduce the risk of eGFR decline, ESKD, CV death, and HHF	EMPA should not be initiated for glycemic control in patients with an eGFR <30 mL/min/1.73 m²	Ertugliflozin is not recommended for use in patients with an eGFR <45 mL/min/1.73 m²
Recommendations Regarding Missed Dose	If a dose is missed, instruct patients to take the dose as soon as possible Advise patients not to double up the next dose
Dosage Forms and Strengths	100 mg, 300 mg tablets	5 mg, 10 mg tablets	10 mg, 25 mg tablets	5 mg, 15 mg tablets
Contraindications	History of a serious hypersensitivity reaction to INVOKANA, such as anaphylaxis or angioedema [see Warnings and Precautions (5.6) and adverse reactions (6.1, 6.2) of the Prescribing Information].	History of a serious hypersensitivity reaction to dapagliflozin or any of the excipients	Hypersensitivity to EMPA or any of the excipients	Hypersensitivity to ertugliflozin or any of the excipients
Warnings and Precautions	DKA in patients with type 1 diabetes mellitus and other ketoacidosis Lower limb amputation Volume depletion Genitourinary infections, including urosepsis, pyelonephritis, necrotizing fasciitis of the perineum (Fournier’s gangrene), and genital mycotic infections Hypoglycemia with concomitant use with insulin or insulin secretagogues Hypersensitivity reactions Bone fracture	DKA in patients with type 1 diabetes mellitus and other ketoacidosis Volume depletion Genitourinary infections, including urosepsis, pyelonephritis, necrotizing fasciitis of the perineum (Fournier’s gangrene), and genital mycotic infections Hypoglycemia with concomitant use with insulin and insulin secretagogues	DKA in patients with type 1 diabetes mellitus and other ketoacidosis Volume depletion Genitourinary infections, including urosepsis, pyelonephritis, necrotizing fasciitis of the perineum (Fournier’s gangrene), and genital mycotic infections Hypoglycemia Lower limb amputation Hypersensitivity reactions	DKA in patients with type 1 diabetes mellitus and other ketoacidosis Lower limb amputation Volume depletion Genitourinary infections, including urosepsis, pyelonephritis, necrotizing fasciitis of the perineum (Fournier’s gangrene), and genital mycotic infections Hypoglycemia with concomitant use with insulin or insulin secretagogues
Adverse Reactions and Drug-Drug Interactions
Most Common (≥5%) Adverse Reactions in Pooled PBO-Controlled Studies	Female genital mycotic infections Urinary tract infections Increased urination	Female genital mycotic infections Nasopharyngitis Urinary tract infections	Urinary tract infection Female genital mycotic infections	Female genital mycotic infections
Other Adverse Reactions (≥2%) in Pooled PBO-Controlled Studies	Male genital mycotic infections Vulvovaginal pruritus Thirst Constipation Nausea	Back pain Increased urination Male genital mycotic infections Nausea Influenza Dyslipidemia Constipation Discomfort with urination Pain in extremity	Upper respiratory tract infection Increased urination Dyslipidemia Arthralgia Male genital mycotic infections Nausea	Male genital mycotic infections Urinary tract infections Headache Vaginal pruritus Increased urination Nasopharyngitis Back pain Weight decreased Thirst
Additional Adverse Reactions from Clinical Studies Experience	Please refer to the full prescribing information for more information	Please refer to the full prescribing information for more information	Please refer to the full prescribing information for more information	Please refer to the full prescribing information for more information
Drug-Drug Interactions	UGT enzyme inducers (eg, rifampin, phenytoin, phenobarbital, ritonavir): CANA exposure reduced UGT enzyme inducer and patients with eGFR ≥60 mL/min/1.73 m²: consider increasing dose from 100 mg once daily to 200 mg (taken as two 100 mg tablets) once daily in patients currently tolerating 100 mg. The dose may be increased to 300 mg once daily in patients currently tolerating 200 mg who require additional glycemic control UGT enzyme inducer and patients with eGFR <60 mL/min/1.73 m²: consider increasing dose from 100 mg once daily to 200 mg once daily in patients currently tolerating 100 mg. Consider adding another AHA in patients who require additional glycemic control Digoxin: Monitor patients taking INVOKANA with concomitant digoxin for a need to adjust the dosage of digoxin Lithium: Concomitant use may decrease serum lithium levels; monitor serum lithium levels more frequently during INVOKANA initiation and dosage changes Positive urine glucose test: alternative method to monitor glycemic control recommended Interference with 1,5-AG assay: alternative method to monitor glycemic control recommended	Insulin or insulin secretagogues (eg, sulfonylurea): concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of hypoglycemia Lithium: monitor serum lithium levels more frequently during dapagliflozin initiation and dosage changes Positive urine glucose test: alternative method to monitor glycemic control recommended Interference with 1,5-AG assay: alternative method to monitor glycemic control recommended	Diuretics: correct volume depletion before EMPA initiation; monitor volume depletion and renal function after treatment initiation Insulin or insulin secretagogues (eg, sulfonylurea): concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of hypoglycemia Lithium: monitor serum lithium levels more frequently during EMPA initiation and dosage changes Positive urine glucose test: alternative method to monitor glycemic control recommended Interference with 1,5-AG assay: alternative method to monitor glycemic control recommended	Insulin or insulin secretagogues: concomitant use may require lower doses of insulin or the insulin secretagogue to reduce the risk of hypoglycemia Lithium: monitor serum levels more frequently during ertugliflozin initiation and dosage changes Positive urine glucose test: alternative method to monitor glycemic control recommended Interference with 1,5-AG assay: alternative method to monitor glycemic control recommended
Use in Specific Populations
Use in Pregnancy	Not recommended during the second and third trimesters of pregnancy
Use in Nursing Mothers	Discontinue drug or nursing
Use in Pediatrics	For patients aged ≥10 years: INVOKANA safety profile similar to that in adults with T2DM. Efficacy and safety of INVOKANA not established in pediatric patients to reduce the risk of: MACE in patients with T2DM and established CVD ESKD, doubling of serum creatinine, CV death, and HHF in patients with T2DM and diabetic nephropathy with albuminuria >300 mg/day Efficacy and safety for glycemic control not established in pediatric patients with T2DM aged <10 years	Efficacy and safety of dapagliflozin as an adjunct to diet and exercise to improve glycemic control in T2DM have been established in pediatric patients aged ≥10 years: dapagliflozin safety profile in pediatric patients was similar to that in adults Efficacy and safety for glycemic control not established in pediatric patients with T2DM aged <10 years Efficacy and safety of dapagliflozin not established in pediatric patients to reduce the risk of sustained eGFR decline, ESKD, CV death, and HHF in patients with CKD at risk of progression CV death, HHF, and urgent heart failure visit in patients with heart failure HHF in patients with T2DM and either established CV disease or multiple CV risk factors	Efficacy and safety of EMPA as an adjunct to diet and exercise to improve glycemic control in T2DM have been established in pediatric patients aged ≥10 years The safety profile of pediatric patients treated with EMPA was similar to that observed in adults with T2DM, with the exception of hypoglycemia risk, which was higher in pediatric patients treated with EMPA regardless of concomitant insulin use Efficacy and safety of EMPA not established in pediatric patients to reduce the risk of CV death and HHF in patients with heart failure sustained eGFR decline, ESKD, CV death, and HHF in patients with CKD at risk of progression CV death in patients with T2DM and established CVD	Safety and effectiveness in age <18 years not established
Use in Geriatrics	Higher incidence of adverse reactions related to reduced intravascular volume, particularly with the 300 mg daily dose	No dosage adjustment is recommended based on age Higher incidence of adverse reaction of hypotension	Higher incidence of adverse reactions related to volume depletion and UTI Diminished glycemic efficacy in elderly patients with renal impairment	No dosage adjustment is recommended based on age Higher incidence of adverse reactions related to volume depletion
Use in Renal Impairment	Moderate renal impairment (eGFR 30 to <50 mL/min/1.73 m²): Less overall glycemic efficacy and transient increases in serum potassium Patients with renal impairment may also be more likely to experience hypotension and may be at higher risk for acute kidney injury INVOKANA is limited to 100 mg once daily at eGFR 30 to <60 mL/min/1.73 m² Efficacy and safety studies with INVOKANA did not enroll patients with ESKD on dialysis or patients with an eGFR <30 mL/min/1.73 m²	Moderate renal impairment: Patients with diabetes and renal impairment may be more likely to experience hypotension and may be at a higher risk for acute kidney injury secondary to volume depletion Higher incidence of bone fractures compared to placebo among patients with eGFR 30 to <60 mL/min/1.73 m² Dapagliflozin use for glycemic control not recommended in patients without established CV disease or CV risk factors when eGFR is <45 mL/min/1.73 m² Safety and efficacy in patients on dialysis or in patients with severe renal impairment are not established (<25 mL/min/1.73 m²)	Moderate renal impairment: Decreased glucose lowering benefit Increased risks of renal impairment, volume depletion adverse reactions and urinary tract infection-related adverse reactions with worsening renal function EMPA use for glycemic control not recommended in patients without established CV disease or CV risk factors when eGFR is <30 mL/min/1.73 m² Safety and efficacy in patients on dialysis or in patients with severe renal impairment (<20 mL/min/1.73 m²) are not established	Patients with stage 3 CKD (eGFR ≥30 to <60 mL/min/1.73 m²) did not show improvement in glycemic control No dosage adjustment is needed in patients with eGFR ≥45 mL/min/1.73 m².
Use in Hepatic Impairment	No dosage adjustment in patients with mild or moderate hepatic impairment INVOKANA use not studied in patients with severe hepatic impairment and is therefore not recommended	No dose adjustments for patients with mild, moderate, or severe hepatic impartment. Assess risk vs benefit in severe hepatic impairment as safety and efficacy not evaluated	May be used in patients with hepatic impairment	No dosage adjustment for mild or moderate hepatic impairment Ertugliflozin use not studied in patients with severe hepatic impairment and is therefore not recommended
Clinical Pharmacology
Mechanism of Action	SGLT2 inhibitor; reduces reabsorption of filtered glucose and lowers the RT_G, and thereby increases UGE
UGE	~100 g/day^k	~70 g/day	EMPA 10 mg: ~64 g/day EMPA 25 mg: ~78 g/day	Dose-dependent increases in UGE were observed in healthy subjects and in patients with T2DM following single- and multiple-dose administration of ertugliflozin
Caloric Loss^a (1 g =~4 kcal)	~400 kcal/day	~280 kcal/day	~256 - 312 kcal/day	Not specified
Food Effects & PK/PD	INVOKANA may be taken with or without food. Co-administration of a high-fat meal with CANA had no effect on the PK of CANA. In single-dose studies in healthy and type 2 diabetic subjects, treatment with CANA 300 mg before a mixed-meal delayed intestinal glucose absorption and reduced PPG. Glucose malabsorption was not reported.⁶^,⁷ Based on the potential to reduce postprandial plasma glucose excursions due to delayed intestinal glucose absorption, it is recommended that INVOKANA be taken before the first meal of the day	Administration of dapagliflozin with a high-fat meal decreases its C_max by up to 50% and prolongs T_max by approximately 1 hour but does not alter AUC as compared with the fasted state. These changes are not considered to be clinically meaningful and dapagliflozin can be administered with or without food	Administration of EMPA 25 mg after intake of a high-fat and high-calorie meal resulted in slightly lower exposure; AUC decreased by approximately 16% and C_max decreased by approximately 37%, compared to fasted condition. The observed effect of food on EMPA PK was not considered clinically relevant and EMPA may be administered with or without food	Administration of ertugliflozin with a high-fat meal and high-calorie meal decreases ertugliflozin C_max by 29% and prolongs T_max by 1 hour but does not alter AUC as compared with the fasted state. These changes are not considered to be clinically meaningful and ertugliflozin may be administered with or without food
PK	Half-life (t_1/2): 10.6 hours and 13.1 hours for the 100 mg and 300 mg doses, respectively Metabolism: Oglucuronidation is the major metabolic elimination pathway for CANA, which is mainly glucuronidated by UGT1A9 and UGT2B4. CYP3A4-mediated (oxidative) metabolism is minimal (approximately 7%) in humans Excretion: ~33% excreted in urine Patients ≥10 years: PK and PD of INVOKANA similar to that in adults Patients with renal impairment: CANA C_max not affected; removal by hemodialysis negligible	Half-life (t_1/2): approximately 12.9 hours for 10 mg dose Metabolism: The metabolism of dapagliflozin is primarily mediated by UGT1A9; CYP-mediated metabolism is a minor clearance pathway in humans Excretion: Dapagliflozin and related metabolites are primarily eliminated via the renal pathway	Half-life (t_1/2): 12.4 hours Metabolism: Primary route suggested to be glucuronidation by UGT2B7, UGT1A3, UGT1A8, and UGT1A9. No major metabolites of EMPA were detected in human plasma and the most abundant metabolites were three glucuronide conjugates (2-O-, 3-O-, and 6-O-glucuronide) Excretion: ~95.6% eliminated in feces (41.2%; majority as unchanged drug) or urine (54.4%; approximately half as unchanged drug)	Half-life (t_1/2): Approximately 16.6 hours Metabolism: The primary route of metabolism is via UGT1A9 and UGT2B7-mediated O-glucuronidation. CYP-mediated metabolism is minimal (12%) Excretion: ~40.9% in feces (33.8% unchanged); ~50.2% excreted in urine (1.5% unchanged)
Clinical Studies Overview
Clinical Studies: Glycemic Control Trials in Adults with T2DM	Monotherapy Initial therapy in combo with metformin XR In combo with metformin, sulfonylurea, metformin + sulfonylurea, metformin + a thiazolidinedione (ie, pioglitazone), or insulin (± other AHAs) Vs sitagliptin + metformin and Vs sitagliptin with each added onto metformin and sulfonylurea Vs glimepiride, each added onto metformin In adults 55 to 80 years of age In patients with moderate renal impairment	Monotherapy Initial therapy in combo with metformin XR Vs glipizide added onto metformin Add-on combination with metformin or glimepiride or metformin + sulfonylurea or pioglitazone or DPP4 inhibitor (± metformin) or insulin (± other oral AHAs) In combo with a GLP-1 agonist (exenatide extended-release) added-on to metformin Monotherapy in patients with moderate renal impairment	Monotherapy Add-on combination with metformin or metformin + sulfonylurea or linagliptin + metformin or pioglitazone (± metformin) or insulin (± metformin and/or sulfonylureas) or MDI insulin (± metformin) Vs glimepiride, each added onto metformin Monotherapy in patients with mild, moderate, and severe renal impairment	Monotherapy Add-on combination with metformin or metformin and sitagliptin or sitagliptin or insulin (±metformin) or metformin and sulfonylurea VS glimepiride added onto metformin In combo with sitagliptin and vs sitagliptin, as add-on to metformin In combo with insulin (±metformin) Add-on combo with metformin and sulfonylurea Monotherapy in patients with moderate renal impairment Monotherapy in patients with established CV disease
Clinical Studies: Glycemic Control in Pediatric Patients Aged ≥10 years with T2DM	Add-on to diet and exercise, metformin HCl (≥1,000 mg per day or maximally tolerated dosage), insulin, or a combination of metformin HCl and insulin N=171 (INVOKANA, n=84; PBO, n=87)	Patients aged 10-17 years Add-on to metformin, insulin, or a combination of metformin and insulin Dapagliflozin (5 mg and 10 mg), n=81; PBO, n=76	Patients aged 10-17 years Monotherapy or add-on to metformin with or without insulin EMPA, n=52; DPP4 inhibitor, n=52; PBO, n=53	None specified
Clinical Studies: CV Outcomes in Patients with T2DM and Atherosclerotic CVD	Integrated analysis of 2 trials (CANVAS and CANVAS-R) evaluated INVOKANA vs PBO, each added to and used concomitantly with SOC treatments for diabetes and atherosclerotic CVD in patients with established CVD or ≥2 risk factors for CVD CANA (100 mg and 300 mg), N=5795 PBO, N=4347	DECLARE-TIMI 58⁸ evaluated dapagliflozin vs PBO, each added to SOC for T2DM and atherosclerotic CVD in patients with established CVD or multiple risk factors for CVD Dapagliflozin 10 mg, N=8582 PBO, N=8578	EMPA-REG OUTCOME study evaluated EMPA vs PBO, each added to and used concomitantly with SOC treatments for diabetes and atherosclerotic CVD in patients with established, stable, atherosclerotic CVD EMPA, N=4687 PBO, N=2333	None specified
Clinical Studies: Renal and CV Outcomes in Patients with Diabetic Nephropathy and Albuminuria	CREDENCE compared CANA with PBO in patients with T2DM, an eGFR ≥30 to <90 mL/min/1.73 m², and albuminuria (urine albumin/creatinine >300 to ≤5000 mg/g) who were receiving SOC, including a maximum-tolerated, labeled daily dose of an ACEi or ARB Primary objective was to assess the efficacy of CANA vs PBO in reducing the composite endpoint of ESKD, doubling of serum creatinine, and renal or CV death CANA 100 mg, N=2202 PBO, N=2199	None specified	None specified	None specified
Study Durations	Ranged from 18 to 26 weeks for PBO-controlled studies (not including extension periods) 52 weeks for active-controlled studies vs sitagliptin and vs glimepiride (not including extension periods) Mean exposure duration of 149 weeks in the integrated analysis of CV outcomes trials (mean exposure 4.3 years in CANVAS and 1.8 years in CANVAS-R). Patients were followed up to 338 weeks as shown in Kaplan-Meier curve depicting time to first occurrence of MACE in the integrated analysis (see Figure 3 in full prescribing information) The median follow-up duration for the 4401 randomized subjects within CREDENCE was 137 weeks	24 weeks for PBO-controlled studies 52 weeks for active-controlled study vs glipizide Median exposure of 4.2 years in DECLARE-TIMI 58⁸	24 weeks for PBO-controlled studies 52 weeks for active-controlled vs glimepiride 78 weeks for PBO-controlled combo insulin study Median 3.1 years for CV outcomes trial	52 weeks for active-controlled vs glimepiride 26 weeks for active-controlled vs and add-on to sitagliptin study 3 years (median) for PBO-controlled study in patients with established CV disease; 26 weeks for other PBO-controlled studies
Efficacy
HbA1C - Primary Endpoint
Monotherapy, LSM change from BL (%)	100 mg (BL 8.06): 0.77 300 mg (BL 8.01): -1.03 PBO (BL 7.97): +0.14	5 mg (BL 7.8): -0.8 10 mg (BL 8.0): -0.9 PBO (BL 7.8): -0.2	10 mg (BL 7.9): -0.7 25 mg (BL 7.9): -0.8 PBO (BL 7.9): 0.1	5 mg (BL 8.2): -0.7 15 mg (BL 8.4): -0.8 PBO (BL 8.1): -0.2
Initial Therapy with Combination Metformin (XR), LSM change from BL (%)	Initial therapy combo metformin XR (inclusion HbA1C 7.5-12%): 100 mg (BL 8.8): -1.37 300 mg (BL 8.8): -1.42 100 mg/metformin XR (BL 8.8): -1.77 300 mg/metformin XR (BL 8.9): -1.78 MET XR (BL 8.8): -1.30	5 mg initial therapy combo metformin XR (inclusion HbA1C 7.5 to 12%): 5 mg + metformin XR (BL 9.2): -2.1 5 mg + PBO (BL 9.1): -1.2 Metformin XR + PBO (BL 9.1): -1.4 10 mg initial therapy combo metformin XR (inclusion HbA1C 7.5-12%): 10 mg + metformin XR (BL 9.1): -2.0 10 mg + PBO (BL 9.0): -1.5 Metformin XR + PBO (BL 9.0): -1.4	None specified	None specified
Studies/Analyses with High BL HbA1C, LSM change from BL (%)	Monotherapy Subgroup Analysis (HbA1C ≥9.0%):⁹ 100 mg: -1.29 300 mg: -1.83 PBO: -0.18 Monotherapy substudy (Inclusion HbA1C >10 to ≤12%):⁹ 100 mg (BL 10.6): -2.1 300 mg (BL 10.6): -2.6 INVOKANA vs sitagliptin, combo metformin + sulfonylurea (BL HbA1C ≥9% Subgroup Analysis):¹⁰ INVOKANA 300 mg: -1.99 Sitagliptin 100 mg: -1.44 Initial therapy combo metformin XR (Inclusion HbA1C 7.5-12%): See Initial Therapy with Combination Metformin XR	5 mg initial therapy combo metformin XR (inclusion HbA1C 7.5-12%): 5 mg + metformin XR (BL 9.2): -2.1 5 mg + PBO (BL 9.1): -1.2 Metformin XR + PBO (BL 9.1): -1.4 10 mg initial therapy combo metformin XR (inclusion HbA1C 7.5-12%): 10 mg + metformin XR (BL 9.1): -2.0 10 mg + PBO (BL 9.0): -1.5 Metformin XR + PBO (BL 9.0): -1.4	None specified	None specified
HbA1C Across Multiple Add-on Combo AHA Studies^b, LSM change from BL (%), range	100 mg (BL 7.78-8.33): -0.7 to -0.89 300 mg (BL 7.79-8.28): -0.79 to -1.06 PBO (BL 7.8-8.49): -0.26 to 0.04 Active comparators (BL 7.83 -8.13): -0.66 to -0.81	5 mg (BL 8.1-8.6): -0.6 to -0.8 10 mg (BL 7.7-8.6): -0.45 to -1.0 PBO (BL 7.8-8.5): -0.4 to +0.04 Active comparator (BL 7.7): -0.5	10 mg (BL 7.9-8.3): -0.4 to -0.8 25 mg (BL 7.9-8.3): -0.6 to -0.8 PBO (BL 7.9-8.2): 0.1 to -0.2 Active comparator (BL 7.9): -0.7	5 mg (BL 7.8-8.1): -0.5 to -0.7 15 mg (BL 7.8-8.0): -0.5 to -0.8 PBO (BL 8.0-8.4): -0.2 to -0.3 Active comparator (BL 7.8): -0.6
HbA1C in Pediatric Patients in Combination with Metformin and/or Insulin, LSM change from BL (%)	CANA (BL 7.8): -0.38^o PBO (BL 8.3): 0.34	5 mg and 10 mg (BL 8.2): -0.6 PBO (BL 8.0): 0.4	10 mg and 25 mg (BL 8.0): -0.2 PBO (BL 8.1): 0.7	None specified
MACE - Primary Endpoint
Composite of CV death, nonfatal MI, nonfatal stroke	CANA: 585 (9.2%) PBO: 426 (10.4%) HR (95% CI): 0.86 (0.75, 0.97)	Dapagliflozin: 756 (8.8%)⁸ PBO: 803 (9.4%) HR (95% CI): 0.93 (0.84, 1.03)	EMPA: 490 (10.5%) PBO: 282 (12.1%) HR (95% CI): 0.86 (0.74, 0.99)	ERTU: 653 (11.9%) PBO: 327 (11.9%) HR (95% CI): 0.97 (0.85, 1.11)
Nonfatal MI	CANA: 215 (3.4%) PBO: 159 (3.9%) HR (95% CI): 0.85 (0.69, 1.05)	Dapagliflozin: 393 (4.6%) PBO: 441 (5.1%) HR (95% CI): 0.89 (0.77, 1.01)	EMPA: 213 (4.5%) PBO: 121 (5.2%) HR (95% CI): 0.87 (0.70, 1.09)	ERTU: 310 (5.6%) PBO: 148 (5.4%) HR (95% CI): 1.04 (0.86, 1.27)
Nonfatal stroke	CANA: 158 (2.5%) PBO: 116 (2.8%) HR (95% CI): 0.90 (0.71, 1.15)	Dapagliflozin: 235 (2.7%) PBO: 231 (2.7%) HR (95% CI): 1.01 (0.84, 1.21) ischemic stroke	EMPA: 150 (3.2%) PBO: 60 (2.6%) HR (95% CI): 1.24 (0.92, 1.67)	ERTU: 157 (2.9%) PBO: 78 (2.8%) HR (95% CI): 1.00 (0.76, 1.32)
CV death	CANA: 268 (4.1%) PBO: 185 (4.6%) HR (95% CI): 0.87 (0.72, 1.06)	Dapagliflozin: 245 (2.9%) PBO: 249 (2.9%) HR (95% CI): 0.98 (0.82, 1.17)	EMPA: 172 (3.7%) PBO: 137 (5.9%) HR (95% CI):: 0.62 (0.49, 0.77)	ERTU: 341 (6.2%) PBO: 184 (6.7%) HR (95% CI): 0.92 (0.77, 1.11)
Time to first occurrence of ESKD (eGFR <15 mL/min/1.73 m², initiation of chronic dialysis, or renal transplant), doubling of serum creatinine, and renal or CV death - Primary Endpoint
Composite of ESKD, doubling of serum creatinine, renal death, or CV death	CANA: 245 (11.1%) PBO: 340 (15.5%) HR: 0.70 (0.59, 0.82)ⁿ	None specified	None specified	None specified
ESKD	CANA: 116 (5.3%) PBO: 165 (7.5%) HR: 0.68 (0.54, 0.86)	None specified	None specified	None specified
Doubling of serum creatinine	CANA: 118 (5.4%) PBO: 188 (8.5%) HR: 0.60 (0.48, 0.76)	None specified	None specified	None specified
Renal death	CANA: 2 (0.1%) PBO: 5 (0.2%) HR: --	None specified	None specified	None specified
CV death	CANA: 110 (5.0%) PBO: 140 (6.4%) HR (95% CI): 0.78 (0.61, 1.00)	None specified	None specified	None specified
Selected Prespecified Secondary Endpoints
Systolic Blood Pressure, mean change from BL, range	-2.6 to -6.6 mmHg^c	-2.8 to -5.3 mmHg^d	-3.6 mmHg (vs glimepiride study) PBO-adjusted mean range: 2.6 to -4.8 mmHgⁱ	-3.8 to -5.7 mmHg^l
Body Weight, mean change from BL, range	-1.8 to -4.7%^e,f	+0.1 to -3.3 kg^g,h	-1.4 to -3.9%^e,j	-2.6 to -3.2 kg^g,m
Abbreviations: 1,5-AG, 1,5-anhydroglucitol; ACEi, angiotensin-converting enzyme inhibitor; AHA, antihyperglycemic agent; ARB, angiotensin receptor blocker; AUC, area under the curve; BL, baseline; CANA, canagliflozin; CI, confidence interval; C_max, maximum plasma concentration; CKD, chronic kidney disease; combo, combination; CV, cardiovascular; CVD, cardiovascular disease; CYP, Cytochrome P450; DPP4, Dipeptidyl peptidase 4; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; EMPA, empagliflozin; ESKD, end-stage kidney disease; ESRD, end-stage renal disease; GLP-1, glucagon-like peptide 1; HbA1C, hemoglobin A1C; HHF, hospitalization for heart failure; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; LSM, least-squares mean; MACE, major adverse cardiovascular events; MI, myocardial infarction; NYHA, New York Heart Association; PBO, placebo; PD, pharmacodynamics; PK, pharmacokinetics; PPG, postprandial glucose; RT_G, renal threshold for glucose; SGLT1, sodium-glucose cotransporter-1; SGLT2, sodium-glucose cotransporter-2; SOC, standard of care; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; T_max, time to maximum plasma concentration; UGE, urinary glucose excretion; UGT, UDP-glucuronosyl transferase; UTI, urinary tract infection; XR, extended-release. Note: Difference in LSM UGE_0-24h placebo-corrected change from baseline to week 4: Ertugliflozin 5 mg: ~64 g/day¹¹;Based on the log-linear regression of change from baseline in 24-hour UGE versus BSA-unnormalized eGFR, the predicted mean change from baseline in 24-hour UGE values on day 1 for T2DM subjects.Ertugliflozin 15 mg, eGFR 105 mL/min: ~69 g/day; ertugliflozin 15 mg, eGFR 75 mL/min: ~39 g/day¹²; estimated caloric loss: ~156-276 kcal/day^aaCalculated based on 1 g of glucose excreted in the urine (UGE) equates to approximately 4 kcal of energy.⁹See UGE section for grams excreted. ^bIncludes add-on combination placebo- and active-controlled studies from Prescribing Information, excluding monotherapy studies (INVOKANA, dapagliflozin, EMPA, and ertugliflozin) and initial therapy in combination with metformin XR studies (dapagliflozin). ^cStudies included: monotherapy, add-on combination therapy with metformin, active-controlled study vs sitagliptin (each as add-on to metformin and sulfonylurea), add-on combination therapy with metformin and pioglitazone, add-on combination therapy with insulin (± other AHAs). ^dStudies included: add-on combination with metformin, active-controlled study vs glipizide (each as add-on to metformin), add-on combination therapy with a sulfonylurea, add-on combination therapy with a thiazolidinedione, add-on combination therapy with insulin. ^eReported in the full Prescribing Information as percent change in body weight from baseline. ^fStudies included: monotherapy, add-on combination therapy with metformin, vs glimepiride (each as add-on to metformin), add-on combination therapy with sulfonylurea, add-on combination therapy with metformin and sulfonylurea, active-controlled study vs sitagliptin (each as add-on to metformin and sulfonylurea), add-on combination therapy with metformin and pioglitazone, add-on combination therapy with insulin (± other AHAs). ^gReported in the full Prescribing Information as change in kilograms from baseline. ^hStudies included: initial combination therapy with metformin XR, add-on combination with metformin, active-controlled study vs glipizide (each as add-on to metformin), add-on combination therapy with other AHAs (sulfonylurea, thiazolidinedione, DPP4 Inhibitor ± metformin, insulin ± up to 2 Oral AHAs). ⁱStudies included: monotherapy and add-on combination therapy with metformin. ^jStudies included: monotherapy, add-on combination therapy with metformin, add-on combination therapy with metformin and sulfonylurea, active-controlled study vs glimepiride in combination with metformin, add-on combination therapy with pioglitazone with or without metformin, and add-on combination with insulin with or without metformin and/or sulfonylureas. ^kIncreases in mean UGE with either 100 mg or 300 mg of CANA. ^lStudies included: add-on combination with metformin and add-on combination with metformin and sitagliptin. ^mStudies included: monotherapy, add-on combination therapy with metformin, active-controlled study vs glimepiride (each as add-on to metformin), add-on combination with metformin and sitagliptin. ⁿP value <0.0001. ^oMultiple imputation using retrieved dropout approach with 1000 iterations for missing data (CANA, n=7 [8.3%]; placebo, n=7 [8.1%] for HbA1C and CANA, n=9 [10.7%]; placebo, n=7 [8.1%] for FPG).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 28 August 2026.

References

Show

1	Sha S, Polidori D, Farrell K, et al. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study. Diabetes Obes Metab. 2015;17(2):188-197.
2	INVOKANA (canagliflozin) [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf
3	FARXIGA (dapagliflozin) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/0be9cb1b-3b33-41c7-bfc2-04c9f718e442/0be9cb1b-3b33-41c7-bfc2-04c9f718e442_viewable_rendition__v.pdf
4	JARDIANCE (empagliflozin) [Prescribing Information]. Indianapolis, IN: Boehringer Ingelheim Pharmaceuticals, Inc; https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf
5	STEGLATRO (ertugliflozin) [Prescribing Information]. Whitehouse Station, NJ: Merck & Co. Inc; https://www.merck.com/product/usa/pi_circulars/s/steglatro/steglatro_pi.pdf
6	Stein P, Berg JK, Morrow L, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism. 2014;63(10):1296-1303.
7	Polidori D, Sha S, Mudaliar S, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013;36(8):2154-2161.
8	Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
9	Stenlöf K, Cefalu WT, Kim KA, et al. 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.
10	Schernthaner G, Gross JL, Rosenstock J, et al. 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. Diabetes Care. 2013;36(9):2508-2515.
11	Amin NB, Wang X, Mitchell JR, et al. Blood pressure‐lowering effect of the sodium glucose co‐transporter‐2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension. Diabetes Obes Metab. 2015;17(8):805-808.
12	Sahasrabudhe V, Terra SG, Hickman A, et al. The effect of renal impairment on the pharmacokinetics and pharmacodynamics of ertugliflozin in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2017;57(11):1432-1443.

Would you like to clear and leave your conversation? Message history will be lost.

Connect with us

Prescribing Information Comparison of INVOKANA to Other SGLT2 Inhibitors

Summary

Literature Search

References

Live video

Waiting for agent...

Ready to join