Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial

Ingrid Gause-Nilsson (1) , Burkhard Göke (2) , Baptist Gallwitz (3) , Johan Eriksson (4) , Asa Hellqvist (1)

1 AstraZeneca
2 Hospital of the Ludwig Maximilian
3 Department of Medicine IV
4 Unit of General Practice

Aim: 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. Methods and patients: A total of 858 patients (age ≥18 years; glycated haemoglobin [HbA1c] >6.5–10.0%; on stable metformin doses ≥1500mg/day) were randomised 1:1 to saxagliptin 5mg/day or glipizide up-titrated as needed from 5–20mg/day for 52 weeks. The primary objective was to assess if the change from baseline HbA1c achieved with saxagliptin plus metformin was non-inferior to glipizide plus metformin. Results: The per-protocol analysis demonstrated non-inferiority of saxagliptin vs. glipizide; adjusted mean changes from baseline HbA1c were –0.74% vs. –0.80%, respectively; the between-group difference was 0.06% (95% CI, –0.05 to 0.16%). Treatment with saxagliptin vs. glipizide was associated with significantly fewer proportion of patients with hypoglycaemic events (3.0% vs. 36.3%; p<0.0001) and a divergent impact on body weight (adjusted mean change from baseline –1.1kg with saxagliptin vs. 1.1kg with glipizide; p<0.0001). There was a significantly smaller rise in HbA1c (%/wk) from week 24 to 52 with saxagliptin vs. glipizide (0.001% vs. 0.004%; p=0.04) indicating a sustained glycaemic effect beyond week 24. Excluding hypoglycaemic events, the proportion of patients experiencing adverse events (AEs) was similar (60.0% saxagliptin vs. 56.7% glipizide); treatment-related AEs were less common with saxagliptin vs. glipizide (9.8% vs. 31.2%), attributable to the higher frequency of hypoglycaemia in glipizide patients. Discontinuation rates due to AEs were similar (~4%). Conclusion: Saxagliptin plus metformin provided a sustained HbA1c reduction over 52 weeks and was non-inferior to glipizide plus metformin, with reduced body weight and significantly lower risk of hypoglycaemia.

Mots clés: Medicine

Ingrid Gause-Nilsson, Burkhard Göke, Baptist Gallwitz, Johan Eriksson, Asa Hellqvist. Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. International Journal of Clinical Practice, 2010, 64 (12), pp.1619. ⟨10.1111/j.1742-1241.2010.02510.x⟩. ⟨hal-00577009⟩