Once-daily saxagliptin added to metformin provides sustained glycaemic control and is well tolerated over 102 weeks in patients with type 2 diabetes

Diabetes is Australia’s fastest growing chronic disease with approximately 890,000 patients currently diagnosed with diabetes.1By 2031 it is predicted that 3.3 million Australians will have type 2 diabetes mellitus,2thus increasing the demand for treatment. Saxagliptin (SAXA) is a potent selective DPP-4 inhibitor designed for extended inhibition of the DPP-4 enzyme. The long-term efficacy and safety of SAXA added to metformin were assessed in patients with T2D and inadequate glycaemic control (A1C ≥7.0% −≤10.0%) on metformin alone. For the double-blind (DB) short-term (ST) treatment period 743 patients (baseline [BL] A1C 8.0%) were randomized and treated 1:1:1:1 to SAXA 2.5, 5, 10 mg or placebo od + stable metformin dose (1500−2500mg/d) for 24 weeks. Patients who met pre-specified glycaemic rescue criteria during ST treatment period received open-label pioglitazone 15-45 mg + blinded study medication and entered the DB 42-month long-term extension (LTE). Patients completing ST treatment period without rescue were also eligible to enter the 42mo LTE; pioglitazone rescue therapy was also available during the LTE based on prespecified glycaemic criteria. At 102 weeks placebo-subtracted A1C changes from BL (n/N) were -0.62, -0.72, and -0.52 for SAXA 2.5, 5, and 10mg, respectively. The proportion of patients (n/N) discontinued for lack of glycaemic control or rescued for meeting prespecified glycaemic criteria was lower for SAXA. SAXA + metformin was generally well tolerated; AE frequency was 89.6%, 78.0%, and 86.7% for SAXA 2.5, 5, and 10 mg vs. 78.8% for placebo + metformin. Proportion of patients with hypoglycaemia events (all) was 10.4%, 8.9%, and 11.0% for SAXA 2.5, 5, and 10mg vs. 10.1% for placebo + metformin and confirmed hypoglycaemia was infrequent. In summary, in patients with T2D inadequately controlled on metformin alone SAXA added to metformin provided sustained clinically meaningful glycaemic improvements over 102 weeks vs. control and was generally well tolerated with no increase in hypoglycaemia or weight.