1. Sodium-glucose co-transporter 2 (SGLT2) inhibitors work by blocking the reabsorption of filtered glucose in the kidneys. This leads to glucosuria and improved glycemic control.
Benefits seen with SGLT2 inhibitors:
Insulin-independent action
Associated with caloric loss, which could result in potential weight loss
Low incidence of hypoglycemia
Complement action of other antidiabetic agents
Can be used regardless of diabetes duration
Side effects seen with SGLT2 inhibitors:
Repeated urinary tract infections
Genital infections
Increased hematocrit
Decreased blood pressure
One formulation of the SGLT2 inhibitor canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes. 2012;5:
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

2. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
The CANTATA-D2 trial examined the efficacy and safety of canagliflozin vs sitagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.
This 52-week, double-blind, active-controlled, Phase III study enrolled subjects who had A1C ≥7.0% to ≤10.5%, who were randomized 1:1 to
300 mg canagliflozin once daily (n=378)
100 mg sitagliptin once daily (n=378)
The primary efficacy endpoint was change in A1C from baseline to Week 52.
Secondary endpoints included change from baseline in fasting plasma glucose and systolic blood pressure, and percent change from baseline in body weight, triglycerides, and high-density lipoprotein cholesterol (HDL-C).
Canagliflozin and sitagliptin are not indicated for weight loss or antihypertensive or lipid-lowering treatment. One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

3. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
In CANTATA-D2, canagliflozin was noninferior to sitagliptin for A1C lowering.
The primary efficacy endpoint, least-squares mean change in A1C from baseline to Week 52, was -1.03% in the canagliflozin group and -0.66% in the sitagliptin group (least-squares means). The between group difference was (95% confidence interval, to -0.25).
Baseline mean A1C in the trial was 8.1%, and participants’ mean type 2 diabetes duration was 9.6 years.
For information on the design of CANTATA-D2, click here.
One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

4. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
In CANTATA-D2, a significantly greater fasting plasma glucose (FPG) reduction was seen with canagliflozin: least-squares mean change of mg/dL (-1.7 mmol/L) vs -2.2 mg/dL (-0.3 mmol/L) seen with sitagliptin.
The between-group difference was mg/dL (-1.3 mmol/L; P<0.001).
Baseline FPG was mg/dL (9.4 mmol/L) in the canagliflozin group and mg/dL (9.1 mmol/L) in the sitagliptin group.
For information on the design of CANTATA-D2, click here.
One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

5. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
In CANTATA-D2, significantly greater weight loss was seen with canagliflozin: -2.5% reduction (-5.1 lbs) vs 0.3% reduction (0.22 lbs) seen with sitagliptin (least-squares mean percent change).
The between-group difference was -2.8% (-5.29 lbs; P<0.001).
Baseline weight was 198 lbs in the sitagliptin group and 193 lbs in the canagliflozin group.
For information on the design of CANTATA-D2, click here.
Canagliflozin and sitagliptin are not indicated for weight loss. One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

6. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
In CANTATA-D2, canagliflozin-treated subjects had a significant reduction in systolic blood pressure (BP) vs those treated with sitagliptin: -5.1 mm Hg vs 0.9 mm Hg with sitagliptin (least-squares mean). Between group difference: -5.9 mm Hg (95% confidence interval [CI], -7.6 to -4.2; P<0.001).
Greater reductions were also seen in diastolic BP with canagliflozin treatment: -3.0 mm Hg vs -0.3 mm Hg seen with sitagliptin (least-squares mean). Between-group difference: -2.7 mm Hg (95% CI, -3.8 to -1.7).
For information on the design of CANTATA-D2, click here.
Canagliflozin and sitagliptin are not indicated as antihypertensive treatments. One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

7. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
In CANTATA-D2, the following results were seen for lipid values:
A larger increase in LDL-C was seen with canagliflozin: least-squares mean (LSM) percent change of 11.7% vs 5.2% with sitagliptin; between-group difference 6.4% (95% confidence interval [CI], 1.7 to 11.2 [LSM]).
With regard to HDL-C, a LSM percent change of 7.6% was seen with canagliflozin, and a minimal change of 0.6% was seen with sitagliptin (LSM between-group difference: 7.0%; 95% CI, 4.6 to 9.3).
Small increases in non–HDL-C and decreases in triglycerides were seen in both groups.
For information on the design of CANTATA-D2, click here.
Canagliflozin and sitagliptin are not indicated as lipid-lowering treatments. One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.

8. Read more about this study in our Clinical Literature section
Read more about this study in our Clinical Literature section. Click here.
The overall incidence of adverse events in CANTATA-D2 was similar in the canagliflozin and sitagliptin groups. The incidence of urinary tract infections and hypoglycemia was also similar between groups.
A higher rate of genetic mycotic infections and osmotic diuresis (polyuria) was seen among canagliflozin-treated patients.
For information on the design of CANTATA-D2, click here.
One formulation of canagliflozin (INVOKANA™) has been FDA approved as of May 2013.
CANTATA-D2=Canagliflozin Treatment and Trial Analysis—dipeptidyl-peptidase-4 inhibitor
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 Epub ahead of print.
May 2013
Click here to return to CCMDweb.org.
This slide was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.