ONGLYZA (Page 7 of 14)
Combination Therapy
Add-On Combination Therapy with Metformin
A total of 743 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin in patients with inadequate glycemic control (A1C ≥7% and ≤10%) on metformin alone. To qualify for enrollment, patients were required to be on a stable dose of metformin (1500-2550 mg daily) for at least 8 weeks.
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 at their pre-study dose, up to 2500 mg daily. Following the lead-in period, eligible patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo in addition to their current dose of open-label metformin. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with pioglitazone rescue therapy, added on to existing study medications. Dose titrations of ONGLYZA and metformin were not permitted.
ONGLYZA 2.5 mg and 5 mg add-on to metformin provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin (Table 5). Mean changes from baseline for A1C over time and at endpoint are shown in Figure 1. The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 15% in the ONGLYZA 2.5 mg add-on to metformin group, 13% in the ONGLYZA 5 mg add-on to metformin group, and 27% in the placebo add-on to metformin group.
| Efficacy Parameter | ONGLYZA 2.5 mg + Metformin N=192 | ONGLYZA 5 mg + Metformin N=191 | Placebo + Metformin N=179 |
|---|---|---|---|
Hemoglobin A1C (%) | N=186 | N=186 | N=175 |
Baseline (mean) | 8.1 | 8.1 | 8.1 |
Change from baseline (adjusted mean †) | −0.6 | −0.7 | +0.1 |
Difference from placebo (adjusted mean †) | −0.7‡ | −0.8‡ | |
95% Confidence Interval | (−0.9, −0.5) | (−1.0, −0.6) | |
Percent of patients achieving A1C <7% | 37%§ (69/186) | 44%§ (81/186) | 17% (29/175) |
Fasting Plasma Glucose (mg/dL) | N=188 | N=187 | N=176 |
Baseline (mean) | 174 | 179 | 175 |
Change from baseline (adjusted mean †) | −14 | −22 | +1 |
Difference from placebo (adjusted mean †) | −16§ | −23§ | |
95% Confidence Interval | (−23, −9) | (−30, −16) | |
2-hour Postprandial Glucose (mg/dL) | N=155 | N=155 | N=135 |
Baseline (mean) | 294 | 296 | 295 |
Change from baseline (adjusted mean †) | −62 | −58 | −18 |
Difference from placebo (adjusted mean †) | −44§ | −40§ | |
95% Confidence Interval | (−60, −27) | (−56, −24) | |
Figure 1: Mean Change from Baseline in A1C in a Placebo-Controlled Trial of ONGLYZA as Add-On Combination Therapy with Metformin*
*Includes patients with a baseline and week 24 value.Week 24 (LOCF) includes intent-to-treat population using last observation on study prior to pioglitazone rescue therapy for patients needing rescue. Mean change from baseline is adjusted for baseline value.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.