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Study details: Goke et al. 2010 and Goke et al. 2013
This was a 52-week, phase 3b, international, multicentre, randomised, parallel-group, active-controlled, double-blind, non-inferiority trial with a 52-week extension period. The aim of this study was to assess the efficacy and safety of saxagliptin vs. glipizide as add-on therapy to metformin in patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin alone.
Adults with HbA1c > 6.5-10% (on stable metformin >1500 mg/day) were randomised to saxagliptin 5 mg/day (n=428; per protocol n=293) or glipizide titrated from 5 to 20 mg/day (mean total daily dose 15 mg/day; n=430; per protocol n=293) for 52 weeks with a 52-week extension. Patients assigned to saxagliptin plus metformin remained on saxagliptin 5 mg throughout the study. For patients assigned to glipizide plus metformin, glipizide was titrated to an optimal effect [FPG ≤ 110 mg/dl (≤ 6.1 mmol/l)] or the highest tolerated dose during an 18-week titration period. The mean metformin dose was approximately 1900 mg in each treatment group.
The primary efficacy end-point was HbA1c, change from baseline at 52 weeks and was used to assess if saxagliptin plus metformin was non-inferior to glipizide plus metformin. The primary efficacy analysis was conducted on a per-protocol (PP) analysis set. The PP analysis set included patients who completed the 52-week randomised treatment period, had both a baseline and week 52 HbA1C measurement and no significant protocol deviations. Onglyza 5 mg + metformin was considered non-inferior to glipizide + metformin if the upper confidence limit of the estimate was <0.35 at 1 year. After 52 weeks, the saxagliptin and glipizide groups had similar mean reductions from baseline in HbA1c, in the per protocol analysis (-0.74% vs. -0.8%, respectively, mean baseline HbA1C of 7.5% for both groups). The difference (95% confidence interval) between the two treatment arms, based on the per-protocol analysis, was 0.06 (-0.05 to 0.16) at 52 weeks, hence establishing non-inferiority.
Key secondary safety and efficacy end-points include the proportion of patients reporting event of hypoglycaemia over 1 year and the change from baseline body weight at 1 year. Assessment of the long-term safety, tolerability and efficacy of add-on saxagliptin vs. glipizide after 104 weeks was a tertiary objective of the initial 52-week study. End-points included the proportion of patients reporting at least one hypoglycaemic event during 104 weeks of treatment. Confirmed hypoglycaemia was defined as a finger-stick glucose value ≤ 2 8 mmol/l with associated symptoms.