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

• Published in: International journal of clinical practice (Esher) Vol. 64; no. 12; pp. 1619 - 1631
• Main Authors: Göke, B., Gallwitz, B., Eriksson, J., Hellqvist, Å., Gause-Nilsson, I.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley-Blackwell; Hindawi Limited; Wiley
• Subjects: Adamantane - administration & dosage; Adamantane - adverse effects; Adamantane - analogs & derivatives; Aged; Biological and medical sciences; Blood Glucose; Clinical trials; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dipeptides - administration & dosage; Dipeptides - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; General aspects; Glipizide - administration & dosage; Glipizide - adverse effects; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemia; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Male; Medical sciences; Metformin - administration & dosage; Metformin - adverse effects; Middle Aged; Treatment Outcome; Dipeptidyl-peptidase IV; Endocrinopathy; Type 2 diabetes; Human; Enzyme; Enzyme inhibitor; Metabolic diseases; Patient; Glipizide; Randomized controlled trial; Medicine; Peptidases; Hypoglycemic agent; Biguanides; Sulfonamides; Gliptine derivatives; Sulfonylureas; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Clinical trial; Metformin; Saxagliptin
• ISSN: 1368-5031; 1742-1241
• DOI: 10.1111/j.1742-1241.2010.02510.x

Summary Aim:  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. Methods and patients:  A total of 858 patients [age ≥ 18 years; glycated haemoglobin (HbA1c) > 6.5 – 10.0%; on stable metformin doses ≥ 1500 mg/day] were randomised 1 : 1 to saxagliptin 5 mg/day or glipizide up‐titrated as needed from 5 to 20 mg/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 a significantly smaller 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 −1.1 kg with saxagliptin vs. 1.1 kg with glipizide; p < 0.0001). There was a significantly smaller rise in HbA1c (%/week) 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 resulting from AEs were similar (∼4%). Conclusion:  Saxagliptin plus metformin was well tolerated, provided a sustained HbA1c reduction over 52 weeks, and was non‐inferior to glipizide plus metformin, with reduced body weight and a significantly lower risk of hypoglycaemia.