Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial

Aim To compare the long-term safety, tolerability and efficacy of saxagliptin vs. glipizide as add-on therapy to metformin. Methods Adults with glycated haemoglobin (HbA1c) >6.510% (on stable metformin 1500mg/day) were randomised to saxagliptin 5mg/day (n=428) or glipizide titrated from 5 to 20mg/day (mean dose 15mg/day; n=430) for 52weeks with a 52-week extension (NCT00575588). Assessment of the long-term safety, tolerability and efficacy of add-on saxagliptin vs. glipizide after 104weeks was a tertiary objective of the initial 52-week study. Results Saxagliptin was well tolerated during the 104-week period; 67.1% of patients receiving saxagliptin vs. 72.6% receiving glipizide had 1 adverse event (AE), and few patients (4.9% vs. 5.6%) discontinued owing to AEs. Fewer patients treated with saxagliptin experienced hypoglycaemia (3.5% vs. 38.4% with glipizide; difference, 34.9%, 95% CI, 39.8 to 30.0) or confirmed hypoglycaemia (0 vs. 9.1% with glipizide). Weight loss was observed with saxagliptin (1.5kg) vs. weight gain with glipizide (+1.3kg; between-group difference, 2.8kg, 95% CI, 3.32kg to 2.20kg). Change from baseline in HbA1c was 0.41 +/- 0.04% with saxagliptin and 0.35 +/- 0.04% with glipizide (between-group difference, 0.05%, 95% CI, 0.17 to 0.06%). A post hoc analysis showed that the proportion of patients with baseline HbA1c 7% who achieved HbA1c <7% (observed data) at week 104 was 23.1% for saxagliptin+metformin and 22.7% for glipizide+metformin. Discussion and Conclusion A lower risk of hypoglycaemia and reduced body weight were observed with saxagliptin vs. glipizide. No other clinically significant differences were observed between groups in safety profile. No significant between-group differences were observed for reductions in glycaemic parameters. After week 24, a smaller weekly rise in HbA1c was observed with saxagliptin vs. glipizide as add-on therapy to metformin.