Saxagliptin is a potent highly selective long-acting DPP-4 inhibitor developed by Bristol Myers Squibb, in partnership with Astra Zeneca Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes J Med Chem. 2005 Jul 28;48(15):5025-37
Saxagliptin was approved for the treatment of type 2 diabetes, either as monotherapy, or add on combination therapy, in the United States on July 31 2009. Review the saxagliptin prescribing information for physicians. A brief summary of the saxagliptin prescribing information is also provided
A Phase 2 12 week dose-ranging study demonstrated the effiacy of saxagliptin, at doses ranging from 2.5-40 mg (12 weeks) or 100 mg (6 weeks, in patients with type 2 diabetes. Saxagliptin was generally well tolerated, however modest reductions in lymphocyte counts were noted, as outlined in Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes Diabetes Obes Metab. 2008 May;10(5):376-86
A Phase 3 study examined th efficacy and safety of saxagliptin when added to metformin therapy in patients with T2DM. Saxagliptin was well tolerated wjen used at doses ranging from 2.5-10 mg daily and reduced HbA1c by 0.59%. The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes on Metformin Alone Diabetes Care. 2009 Jun 23. [Epub ahead of print]
Early initial combination therapy with saxagliptin and metformin was examined in a 24 week study by Jadzinsky and colleagues. Subjects, ages 18-77 years of age, were randomized to 5 or 10 mg of saxagliptin and an initial 500 mg dose of metformin, titrated up to 2 grams daily after week 1. Mean entry HbA1c ranged from 8-12% with a mean entry A1c of ~9.5%. Combination therapy was more potent then either saxagliptin or metformin alone in regard to reduction of A1c and proportion of patients at goal. Drop out rates were surprisingly high across all arms of the study, ranging from 20-30%. The numbers and types of AEs were similar across all treatment groups, and a small absolute decrease in mean lymphocyte count was observed in saxagliptin-treated patients,however mean lymphocyte counts remained within normal limits, with no clinical sequelae attributable to changes in lymphocyte count. See Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial Diabetes Obes Metab. 2009 Jun;11(6):611-22
Saxagliptin efficacy has also been studied in combination with submaximal doses of SUs, vs. uptitration of SU alone. Patients (ages 18-77) had a mean entry HbA1c of 7.5-10% and were treated with 5 or 10 mg of s saxagliptin in combination with 7.5 mg glyburide vs. glyburide 10-20 mg alone for 24 weeks. The mean dose of gyburide alone was 15 mg daily at the end of the study. More patients (~22%) achieved a target A1c of less than 7% on combination therapy compared to SU therapy (9.1%) alone. The numbers of AEs and hypoglycemic events were comparable across treatment groups and weight gain was slightly but significantly greater in subjects treated with saxagliptin relative to SU-therapy alone(0.7 and 0.8 vs. 0.3 kg). See Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial Int J Clin Pract. 2009 Jul 15. [Epub ahead of print]
Saxagliptin in combination with pioglitazone or rosiglitazone was studied in a 24 week study; patients had a mean entry HbA1c of 7-10.5% on stable TZD therapy. Addition of saxagliptin reduced HbA1c by 0.66 (2.5 mg) or 0.94% (5 mg) from a mean baseline of 8.3%. About 40% of patients achieved a HbA1c of less than 70% on saxagliptin/TZD therapy. Body weight increased in subjects treated with saxagliptin and placebo (1.3 vs. 0.9 kg). See Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone J Clin Endocrinol Metab. 2009 Dec;94(12):4810-9. Epub 2009 Oct 28.