Saxagliptin (SAXA) is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme. The efficacy and safety of SAXA 5 mg add-on therapy to a thiazolidinedione (TZD), metformin (MET), or an intermediate dose of glibenclamide (GLY), was investigated in patients with inadequately controlled (HbA1c>7.0%) type 2 diabetes mellitus (T2DM) in three randomised, double-blind trials (CV181-013, CV181-014 and CV181-040, respectively). Following a placebo run-in period, patients (aged 1877 years) were randomised to receive SAXA 5 mg or placebo once daily plus their stable TZD, MET or GLY dose. Blinded up-titration of GLY was allowed in the GLY-only arm to a maximum daily dose of 15 mg. All studies primary endpoint was HbA1c change from baseline. Changes in fasting plasma glucose (FPG) and postprandial glucose (PPG) were also measured. Baseline characteristics within each study were well balanced across treatment groups. At Week 24, SAXA 5 mg add-on treatment provided significant (P<0.01) reductions from baseline in HbA1c, FPG and PPG area under the curve (AUC), with increased proportions of patients achieving therapeutic glycaemic response (HbA1c<7%), compared with matched controls (Table). In each study, SAXA was well tolerated. SAXA add-on therapy to ongoing TZD, MET or GLY provides significant and clinically meaningful reductions in key parameters of glycaemic control and is well tolerated in patients with inadequately controlled T2DM.
|Add-on to TZD||Add-on to MET||Add-on to GLY|
|SAXA (n=186)||Placebo (n=184)||SAXA (n=191)||Placebo (n=179)||SAXA (n=253)||Placebo (n=267)|
|PPG AUC (mmol·min/l)*||−515||−149||−532||−183||−278||+66|
|*Changes from baseline. All P<0.01 versus placebo group.|
25 - 29 Apr 2009
European Society of Endocrinology