Saxagliptin (SAXA) Effectively Reduces HbA1c and Is Well Tolerated When Added to a Combination of Metformin (MET) and Sulphonylurea (SU)

Robert G. Moses, Sanjay Kalra, Debbie Brook, Jim Sockler, Jayanti Visvanathan, Simon A. Fisher, Wollongong, Australia; Karnal, India; North Ryde, Australia; Drummoyne, Australia; Singapore, Singapore

Combination therapy with MET and SU is common in patients with type 2 diabetes (T2D), and many will require triple oral therapy (TOT). This 24-wk, multicenter, double-blind, phase 3b study evaluated the efficacy and safety of the DPP-4 inhibitor SAXA vs placebo (PBO) as add-on therapy in 257 adults with T2D who had inadequate glycaemic control (HbA1c 7%–10%) after at least 8 wk on dual therapy with MET and SU at stable, maximum tolerated doses. The primary endpoint was change from baseline HbA1c at wk 24. Most baseline characteristics were similar in the SAXA and PBO groups. Mean age, 57.2 vs 56.8 y; mean BMI, 29.4 vs 29.1 kg/m2; white 45.7% vs 44.5%; Asian 54.3% vs 55.5%; mean baseline HbA1c was slightly higher in the SAXA group (8.37% vs 8.19%). A total of 87.6% of patients in the SAXA group and 88.3% in the PBO group completed the study. At wk 24, mean reductions in HbA1c were greater with SAXA than with PBO added to MET and SU: –0.74% vs –0.08%, respectively, with a mean between-group difference of –0.66% (95% CI: –0.86%, –0.47%; P<0.0001; last observations carried forward). TOT including SAXA was well tolerated; 59.7% vs 69.5% of patients receiving SAXA vs PBO, respectively, had ≥1 adverse event (AE). AEs occurring in ≥5% of patients receiving either SAXA or PBO were nasopharyngitis (6.2% vs 9.4%, respectively), diarrhoea (5.4% vs 3.9%), hypertension (5.4% vs 1.6%), dyslipidaemia (3.9% vs 5.5%) and urinary tract infection (3.1% vs 6.3%). Incidences of all reported hypoglycaemia were 10.2% with SAXA and 6.3% with PBO; confirmed hypoglycaemia (symptoms + glucose <50 mg/dL) were 0.8% with SAXA and 0 with PBO. SAXA used in triple oral therapy in patients whose T2D is inadequately controlled on MET and SU effectively improves glycaemic control and is well tolerated.

Supported by: Bristol-Myers Squibb and AstraZeneca

Keywords (Complete): DPP-4 inhibitor, saxagliptin ; triple therapy, metformin ; sulfonylurea, T2DM, glycaemic control