lue and stratification factors
p<0.001
INVOKANA Compared to Sitagliptin, Both as Add-on Combination Therapy With Metformin and Sulfonylurea
A total of 755 patients with type 2 diabetes inadequately controlled on the combination of metformin (greater than or equal to 2,000 mg/day or at least 1,500 mg/day if higher dose not tolerated) and sulfonylurea (near-maximal or maximal effective dose) participated in a 52-week, double-blind, active-controlled study to compare the efficacy and safety of INVOKANA 300 mg versus sitagliptin 100 mg in combination with metformin and sulfonylurea. The mean age was 57 years, 56% of patients were men, and the mean baseline eGFR was 88 mL/min/1.73 m2. Patients already on protocol-specified doses of metformin and sulfonylurea (N=716) entered a 2-week single-blind, placebo run-in period. Other patients (N=39) were required to be on a stable protocol-specified dose of metformin and sulfonylurea for at least 8 weeks before entering the 2-week run-in period. Following the run-in period, patients were randomized to INVOKANA 300 mg or sitagliptin 100 mg as add-on to metformin and sulfonylurea.
As shown in Table 12 and Figure 2, at the end of treatment, INVOKANA 300 mg provided greater HbA1C reduction compared to sitagliptin 100 mg when added to metformin and sulfonylurea (p<0.05). INVOKANA 300 mg resulted in a mean percent change in body weight from baseline of -2.5% compared to +0.3% with sitagliptin 100 mg. A mean change in systolic blood pressure from baseline of -5.06 mmHg was observed with INVOKANA 300 mg compared to +0.85 mmHg with sitagliptin 100 mg.
Table 12: Results from 52−Week Clinical Study Comparing INVOKANA to Sitagliptin in Combination with Metformin and Sulfonylurea *
Efficacy Parameter INVOKANA 300 mg + Metformin and Sulfonylurea(N=377) Sitagliptin 100 mg + Metformin and Sulfonylurea(N=378)
*Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
INVOKANA + metformin is considered non-inferior to sitagliptin + metformin because the upper limit of this confidence interval is less than the pre-specified non-inferiority margin of < 0.3%.
p<0.001
HbA1C (%)
Baseline (mean) 8.12 8.13
Change from baseline (adjusted mean) -1.03 -0.66
Difference from sitagliptin (adjusted mean) (95% CI) † -0.37‡(-0.50; -0.25)
Percent of patients achieving HbA1C < 7% 48 35
Fasting Plasma Glucose (mg/dL)
Baseline (mean) 170 164
Change from baseline (adjusted mean) -30 -6
Difference from sitagliptin (adjusted mean) (95% CI) † -24(-30; -18)
Body Weight
Baseline (mean) in kg 87.6 89.6
% change from baseline (adjusted mean) -2.5 0.3
Difference from sitagliptin (adjusted mean) (95% CI) † -2.8§(-3.3; -2.2)
Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
INVOKANA + metformin is considered non-inferior to sitagliptin + metformin because the upper limit of this confidence interval is less than the pre-specified non-inferiority margin of < 0.3%.
p<0.001
Figure 2: Mean HbA1C Change at Each Time Point (Completers) and at Week 52 Using Last Observation Carried Forward (mITT Population)
Add-on Combination Therap |
