New DPP4 inhibitor launched

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
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 HbA1c level of 8% despite receiving up to 2550mg metformin per day. Addition of saxagliptin 2.5mg, 5mg or 10mg daily reduced HbA1c 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 HbA1c 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, HbA1c 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 HbA1c 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 HbA1c; 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

  1. Onglyza Summary of product characteristics, October 2009.
  2. DeFronzo RA et al. Diabetes Care 2009; 32: 1649-55.
  3. DeFronzo RA et al. Diabetes 2009; 58(Suppl 1): A147, Abstract 547-P.
  4. CHMP Assessment Report for Onglyza. EMEA/H/C/001039

Further information: BMS and AstraZeneca


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