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) > 6.5-10% (on stable metformin ≥ 1500 mg/day) were randomised to saxagliptin 5 mg/day (n = 428) or glipizide titrated from 5 to 20 mg/day (mean dose 15 mg/day; n = 430) for 52 weeks with a 52-week extension (NCT00575588). 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.

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 (-1.5 kg) vs. weight gain with glipizide (+1.3 kg; between-group difference, -2.8 kg, 95% CI, -3.32 kg to -2.20 kg). 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.