Saxagliptin as Add-On Therapy to Insulin in Patients with Type 2 Diabetes

San Diego—A phase 3b trial presented in a poster session at the ADA meeting indicated that adult patients with type 2 diabetes who took 5 mg of saxagliptin once daily as an add-on therapy to insulin (with or without metformin) showed greater improvement in glycemic control compared with a placebo group. The poster was titled Saxagliptin Add-On Therapy Improves Glycemic Control in Patients with Poorly Controlled Type 2 Diabetes on Insulin (INS) Alone or INS Combined with Metformin. Saxagliptin, a dipeptidyl peptidase-4 inhibitor, was approved by the US Food and Drug Administration in July 2009 as an adjunct to diet and exercise to improve blood glucose control in patients with type 2 diabetes. In this placebo-controlled, double-blind study, the authors were interested in determining the safety and effectiveness of saxagliptin as an add-on therapy with insulin for patients who did not gain adequate control taking insulin or insulin plus metformin. They randomized 455 patients with type 2 diabetes and hemoglobin A1c (HbA1c) levels between 7.5% and 11.0% in a 2:1 ratio to take 5 mg of saxagliptin (n=304) or placebo (n=151) once daily for 24 weeks. Each patient also received insulin. In addition, the majority (69%-70%) of patients in both groups took metformin. The demographics and baseline characteristics were similar between the groups. Patients had a mean age of 57 years, had type 2 diabetes for a mean of 12 years, and had a mean HbA1c level of 8.7%. At week 24, patients in the saxagliptin group had a 0.73% reduction in HbA1c level from baseline compared with a 0.32% reduction in the placebo group (P<.0001). There was also a statistically significant difference in the reduction from baseline in the 120-minute postprandial glucose (PPG) in response to a meal tolerance test (27.2 vs 4.2 mg/dL; P=.0016). The change from baseline in the area under the curve from 0 to 180 minutes for PPG during a mixed meal was also significantly lower in the saxagliptin group (P=.0011). Patients in the saxagliptin group had an adjusted mean decrease in fasting plasma glucose from baseline of 10.08 mg/dL compared with a mean decrease of 6.06 mg/dL in the placebo group, but the difference was not significant (P=.3958). In addition, 17.3% of patients who received saxagliptin achieved HbA1c <7% compared with 6.7% of patients who received placebo, but the researchers did not test the statistical significance of that secondary end point. The authors said saxagliptin was well tolerated. The proportion of patients with ≥1 adverse event (AE) was similar in the groups (56.9% in the saxagliptin group vs 59.6% in the placebo group) as was the proportion of patients with ≥1 serious AE (3.9% in the saxagliptin group vs 4.0% in the placebo group). The most common AE was hypoglycemia, which was reported in 18.4% of the saxagliptin patients and 19.9% of the placebo patients. The following AEs were found in ≥5% of patients: urinary tract infection, influenza, and pain in the extremities. According to the authors, a possible limitation occurred if patients changed their insulin dose, which they were advised not to change. The authors said an increase in insulin for patients in the placebo group could decrease the magnitude of the differences between the groups in the efficacy analyses. This study was supported by Bristol-Myers Squibb and AstraZeneca.