ONGLYZA (Page 10 of 14)
Coadministration with Metformin in Treatment-Naive Patients
A total of 1306 treatment-naive patients with type 2 diabetes mellitus participated in this 24-week, randomized, double-blind, active-controlled trial to evaluate the efficacy and safety of ONGLYZA coadministered with metformin in patients with inadequate glycemic control (A1C ≥8% to ≤12%) on diet and exercise alone. Patients were required to be treatment-naive to be enrolled in this study.
Patients who met eligibility criteria were enrolled in a single-blind, 1-week, dietary and exercise placebo lead-in period. Patients were randomized to one of four treatment arms: ONGLYZA 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo, or metformin 500 mg + placebo. The 10 mg saxagliptin dosage is not an approved dosage. ONGLYZA was dosed once daily. In the 3 treatment groups using metformin, the metformin dose was up-titrated weekly in 500 mg per day increments, as tolerated, to a maximum of 2000 mg per day based on FPG. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue as add-on therapy.
Coadministration of ONGLYZA 5 mg plus metformin provided significant improvements in A1C, FPG, and PPG compared with placebo plus metformin (Table 8).
| Efficacy Parameter | ONGLYZA 5 mg + Metformin N=320 | Placebo + Metformin N=328 |
|---|---|---|
| Hemoglobin A1C (%) | N=306 | N=313 |
| Baseline (mean) | 9.4 | 9.4 |
| Change from baseline (adjusted mean †) | −2.5 | −2.0 |
| Difference from placebo + metformin (adjusted mean †) | −0.5‡ | |
| 95% Confidence Interval | (−0.7, −0.4) | |
| Percent of patients achieving A1C <7% | 60%§ (185/307) | 41% (129/314) |
| Fasting Plasma Glucose (mg/dL) | N=315 | N=320 |
| Baseline (mean) | 199 | 199 |
| Change from baseline (adjusted mean †) | −60 | −47 |
| Difference from placebo + metformin (adjusted mean †) | −13§ | |
| 95% Confidence Interval | (−19, −6) | |
| 2-hour Postprandial Glucose (mg/dL) | N=146 | N=141 |
| Baseline (mean) | 340 | 355 |
| Change from baseline (adjusted mean †) | −138 | −97 |
| Difference from placebo + metformin (adjusted mean †) | −41§ | |
| 95% Confidence Interval | (−57, −25) | |
Add-On Combination Therapy with Metformin versus Glipizide Add-On Combination Therapy with Metformin
In this 52-week, active-controlled trial, a total of 858 patients with type 2 diabetes and inadequate glycemic control (A1C >6.5% and ≤10%) on metformin alone were randomized to double-blind add-on therapy with ONGLYZA or glipizide. Patients were required to be on a stable dose of metformin (at least 1500 mg daily) for at least 8 weeks prior to enrollment.
Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin (1500-3000 mg based on their pre-study dose). Following the lead-in period, eligible patients were randomized to 5 mg of ONGLYZA or 5 mg of glipizide in addition to their current dose of open-label metformin. Patients in the glipizide plus metformin group underwent blinded titration of the glipizide dose during the first 18 weeks of the trial up to a maximum glipizide dose of 20 mg per day. Titration was based on a goal FPG ≤110 mg/dL or the highest tolerable glipizide dose. Fifty percent (50%) of the glipizide-treated patients were titrated to the 20-mg daily dose; 21% of the glipizide-treated patients had a final daily glipizide dose of 5 mg or less. The mean final daily dose of glipizide was 15 mg.
After 52 weeks of treatment, ONGLYZA and glipizide resulted in similar mean reductions from baseline in A1C when added to metformin therapy (Table 9). This conclusion may be limited to patients with baseline A1C comparable to those in the trial (91% of patients had baseline A1C <9%).
From a baseline mean body weight of 89 kg, there was a statistically significant mean reduction of 1.1 kg in patients treated with ONGLYZA compared to a mean weight gain of 1.1 kg in patients treated with glipizide (p<0.0001).
| Efficacy Parameter | ONGLYZA 5 mg + Metformin N=428 | Titrated Glipizide + Metformin N=430 |
|---|---|---|
| ||
| Hemoglobin A1C (%) | N=423 | N=423 |
| Baseline (mean) | 7.7 | 7.6 |
| Change from baseline (adjusted mean †) | −0.6 | −0.7 |
| Difference from glipizide + metformin (adjusted mean †) | 0.1 | |
| 95% Confidence Interval | (−0.02, 0.2)‡ | |
| Fasting Plasma Glucose (mg/dL) | N=420 | N=420 |
| Baseline (mean) | 162 | 161 |
| Change from baseline (adjusted mean †) | −9 | −16 |
| Difference from glipizide + metformin (adjusted mean †) | 6 | |
| 95% Confidence Interval | (2, 11)§ | |
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