New DPP4 inhibitor launched

26 November 2009

Bristol Myers-Squibb and AstraZeneca have launched Onglyza (saxagliptin) for add-on therapy in patients with type II diabetes.

Onglyza – once daily add-on therapy for type II diabetes

PHARMACOLOGY

Saxagliptin inhibits dipeptidyl peptidase 4 (DPP4) to prevent the breakdown of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These incretin hormones stimulate insulin secretion and suppress glucagon production; consequently, blood glucose levels fall. Administered as a once daily 5mg dose, saxagliptin maintains potent and selective inhibition of DPP4 activity for 24 hours.¹

CLINICAL STUDIES

A randomised, double-blind, 24-week trial enrolled 743 patients with type II diabetes and a mean HbA_1c level of 8% despite receiving up to 2550mg metformin per day. Addition of saxagliptin 2.5mg, 5mg or 10mg daily reduced HbA_1c level from baseline by a mean of 0.73, 0.83 and 0.72%, respectively, compared with addition of placebo (p<0.0001 for all). Patients receiving saxagliptin were more than twice as likely to achieve an HbA_1c below 7% as those on placebo (p≤0.0001).²

Over the 24-week period, saxagliptin also produced significantly greater reductions than placebo in two other key measures of glycaemic control: fasting plasma glucose level (p<0.0001 for all doses) and 3-hour post-prandial glucose AUC during an oral glucose tolerance test (p<0.0001 for all doses).²

Patients who met pre-specified criteria for (or who did not require) hyperglycaemic rescue therapy during this study were eligible to enter a double-blind extension phase. Results showed that the improvements in glycaemic control achieved with saxagliptin were sustained for up to 102 weeks; compared with the placebo group, HbA_1c reductions from baseline to this time point were 0.62, 0.72 and 0.52% in the saxagliptin 2.5mg, 5mg and 10mg groups, respectively.³

Randomised trials were also conducted to examine the efficacy of saxagliptin in conjunction with a glitazone or a sulfonylurea. In 370 patients with inadequate glycaemic control on pioglitazone or rosiglitazone alone, add-on therapy with saxagliptin 5mg daily produced a greater mean reduction in HbA1c level over 24 weeks than add-on treatment with placebo (p<0.0001). Similarly, saxagliptin was superior to placebo in reducing HbA_1c levels over a 24-week period in 768 patients already receiving glibenclamide (p<0.0001).⁴

Preliminary results have been reported from a randomised, double-blind, 18-week study that compared saxagliptin to sitagliptin in 801 adults with type II diabetes who had inadequate glycaemic control on metformin (≥1500mg daily). Addition of saxagliptin 5mg daily to metformin therapy was noninferior to addition of sitagliptin 100mg daily in reducing HbA_1c; in the per protocol analysis, adjusted mean reductions from baseline were 0.52% and 0.62%, respectively.⁴

In the above trials, the incidence of adverse events in patients treated with saxagliptin 5mg was generally similar to that in patients who received the comparator treatment (i.e. placebo or sitagliptin).¹ Saxagliptin was not associated with increased risks of hypoglycaemia or weight gain.^2,3 The adverse effects most commonly associated with saxagliptin are infections (respiratory, urinary and gastrointestinal), headache and vomiting.¹

Onglyza is not licensed for the treatment of type I diabetes or diabetic ketoacidosis, and has not been studied in combination with insulin.

View Onglyza drug record

REFERENCES