A Pfützner1, E Paz-Pacheco, E Allen, R Frederich, R Chen. 1. Institute for Clinical Research and Development, Mainz, Germany The Medical City, Pasig City, Philippines Bristol-Myers Squibb, Princeton, NJ, USA.
Abstract
AIM: To assess the efficacy and safety of saxagliptin + metformin initial combination therapy compared with saxagliptin or metformin alone over 76 weeks (24-week short-term + 52-week long-term extension) in treatment-naÏve type 2 diabetes mellitus patients with inadequate glycaemic control. METHODS: In this phase 3, parallel-group, double-blind, active-controlled study, 1306 patients 18-77 years of age (HbA1c 8.0-12.0%) were randomized to saxagliptin 5 mg + 500 mg metformin, saxagliptin 10 mg + 500 mg metformin, saxagliptin 10 mg + placebo or 500 mg metformin + placebo. Blinded metformin was titrated during weeks 1-5 of the short-term treatment period in 500 mg/day increments to 2000 mg/day maximum in the metformin-based treatment groups. No titration of metformin was permitted during the long-term treatment period. A total of 888 patients completed the study (76 weeks), 613 without being rescued. Changes in HbA1c, fasting plasma glucose, 120-min postprandial glucose (PPG) and PPG-area under the curve (AUC) from baseline to week 76 were analysed using a repeated-measures model. RESULTS: At 76 weeks, adjusted mean changes from baseline HbA1c (95% CI) for saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin, saxagliptin 10 mg and metformin were -2.31 (-2.44, -2.18), -2.33 (-2.46, -2.20), -1.55 (-1.70, -1.40) and -1.79% (-1.93, -1.65), respectively (post hoc and nominal p < 0.0001 vs. metformin and saxagliptin monotherapies for saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin). The proportions of patients requiring rescue or discontinuation for insufficient glycaemic control were lower for saxagliptin + metformin than for either monotherapy. Little or no attenuation in PPG-AUC or 120-min PPG was observed between weeks 24 and 76 for saxagliptin + metformin, indicating persistent efficacy. Adverse event rates were similar across groups; hypoglycaemic events occurred at a low frequency. CONCLUSION:Saxagliptin + metformin initial combination therapy was well tolerated and produced sustained glycaemic control for up to 76 weeks, with greater improvements in glycaemic parameters compared with either drug alone.
RCT Entities:
AIM: To assess the efficacy and safety of saxagliptin + metformin initial combination therapy compared with saxagliptin or metformin alone over 76 weeks (24-week short-term + 52-week long-term extension) in treatment-naÏve type 2 diabetes mellituspatients with inadequate glycaemic control. METHODS: In this phase 3, parallel-group, double-blind, active-controlled study, 1306 patients 18-77 years of age (HbA1c 8.0-12.0%) were randomized to saxagliptin 5 mg + 500 mg metformin, saxagliptin 10 mg + 500 mg metformin, saxagliptin 10 mg + placebo or 500 mg metformin + placebo. Blinded metformin was titrated during weeks 1-5 of the short-term treatment period in 500 mg/day increments to 2000 mg/day maximum in the metformin-based treatment groups. No titration of metformin was permitted during the long-term treatment period. A total of 888 patients completed the study (76 weeks), 613 without being rescued. Changes in HbA1c, fasting plasma glucose, 120-min postprandial glucose (PPG) and PPG-area under the curve (AUC) from baseline to week 76 were analysed using a repeated-measures model. RESULTS: At 76 weeks, adjusted mean changes from baseline HbA1c (95% CI) for saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin, saxagliptin 10 mg and metformin were -2.31 (-2.44, -2.18), -2.33 (-2.46, -2.20), -1.55 (-1.70, -1.40) and -1.79% (-1.93, -1.65), respectively (post hoc and nominal p < 0.0001 vs. metformin and saxagliptin monotherapies for saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin). The proportions of patients requiring rescue or discontinuation for insufficient glycaemic control were lower for saxagliptin + metformin than for either monotherapy. Little or no attenuation in PPG-AUC or 120-min PPG was observed between weeks 24 and 76 for saxagliptin + metformin, indicating persistent efficacy. Adverse event rates were similar across groups; hypoglycaemic events occurred at a low frequency. CONCLUSION:Saxagliptin + metformin initial combination therapy was well tolerated and produced sustained glycaemic control for up to 76 weeks, with greater improvements in glycaemic parameters compared with either drug alone.
Authors: Anders Gummesson; Haiyan Li; Michael Gillen; John Xu; Mohammad Niazi; Boaz Hirshberg Journal: Clin Drug Investig Date: 2014-11 Impact factor: 2.859
Authors: R J Stevens; R Ali; C R Bankhead; M A Bethel; B J Cairns; R P Camisasca; F L Crowe; A J Farmer; S Harrison; J A Hirst; P Home; S E Kahn; J H McLellan; R Perera; A Plüddemann; A Ramachandran; N W Roberts; P W Rose; A Schweizer; G Viberti; R R Holman Journal: Diabetologia Date: 2012-08-10 Impact factor: 10.122