y With Metformin and Pioglitazone
A total of 342 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 pioglitazone (30 or 45 mg/day) participated in a 26-week, double-blind, placebo-controlled study to eva luate the efficacy and safety of INVOKANA in combination with metformin and pioglitazone. Patients already on protocol-specified doses of metformin and pioglitazone (N=163) entered a 2-week, single-blind, placebo run-in period. Other patients (N=181) were required to be on stable protocol-specified doses of metformin and pioglitazone for at least 8 weeks before entering the 2-week run-in period. Following the run-in period, patients were randomized to INVOKANA 100 mg, INVOKANA 300 mg, or placebo, administered once daily as add-on to metformin and pioglitazone.
At the of end of treatment, INVOKANA 100 mg and 300 mg once daily resulted in a statistically significant improvement in HbA1C (p<0.001 for both doses) compared to placebo when added to metformin and pioglitazone. INVOKANA 100 mg and 300 mg once daily also resulted in a greater proportion of patients achieving an HbA1C less than 7%, in significant reduction in fasting plasma glucose (FPG) and in percent body weight reduction compared to placebo when added to metformin and pioglitazone (see Table 13). Statistically significant (p<0.05 for both doses) mean changes from baseline in systolic blood pressure relative to placebo were -4.1 mmHg and -3.5 mmHg with INVOKANA 100 mg and 300 mg, respectively.
Table 13: Results from 26−Week Placebo-Controlled Clinical Study of INVOKANA in Combination with Metformin and Pioglitazone *
Efficacy Parameter Placebo + Metforminand Pioglitazone(N=115) INVOKANA 100 mg + Metformin and Pioglitazone(N=113) INVOKANA 300 mg + Metformin and Pioglitazone(N=114)
* Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
p<0.001
HbA1C (%)
Baseline (mean) 8.00 7.99 7.84
Change from baseline (adjusted mean) -0.26 -0.89 -1.03
Difference from placebo (adjusted mean) (95% CI) † -0.62‡(-0.81; -0.44) -0.76‡(-0.95; -0.58)
Percent of patients achieving HbA1C < 7% 33 47‡ 64‡
Fasting Plasma Glucose (mg/dL)
Baseline (mean) 164 169 164
Change from baseline (adjusted mean) 3 -27 -33
Difference from placebo (adjusted mean) (95% CI) † -29‡(-37;-22) -36‡(-43;-28)
Body Weight
Baseline (mean) in kg 94.0 94.2 94.4
% change from baseline (adjusted mean) -0.1 -2.8 -3.8
Difference from placebo (adjusted mean) (95% CI) † -2.7‡(-3.6; -1.8) -3.7‡(-4.6;-2.8)
Intent-to-treat population using last observation in study prior to glycemic rescue therapy
Least squares mean adjusted for baseline value and stratification factors
p<0.001
Add-On Combination Therapy With Insulin (With or Without Other Antihyperglycemic Agents)
A total of 1718 patients with type 2 diabetes inadequately controlled on insulin greater than or equal to 30 units/day or insulin in combination with other antihyperglycemic agents participated in an 18-week, double-blind, placebo-controlled substudy of a cardiovascular study to eva luate the efficacy |
