Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea

Objective: To compare safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 30) with exenatide in subjects with type 2 diabetes mellitus (T2DM) not achieving glycemic targets with metformin and sulfonylurea in a randomized, open-label, 24-week trial. Research design and methods: ubjects (N = 372, T2DM>6 months, age >= 18 and <= 80 years, HbA(1c) >= 8%, insulin naive not achieving glycaemic targets, receiving metformin and sulfonylurea) were randomized 1: 1: 1 to receive either BIAsp 30 QD (12 U before supper); BIAsp 30 BID (12 U divided equally between pre-breakfast and pre-supper); or exenatide (5 mu g BID for 4 weeks and 10 mu g BID thereafter). Efficacy (HbA1c, fasting plasma glucose [FPG]) and safety (adverse events and hypoglycemic episodes) were assessed. Results: Glycemic control achieved with both BIAsp 30 BID and BIAsp 30 QD was superior to that with exenatide (BIAsp 30 BID-exenatide: HbA1c difference - 0.91% [95% CI: - 1.23 to - 0.59%] and BIAsp 30 QD-exenatide: difference: - 0.67% [95% CI: - 0.99 to - 0.34%]). At the end of the study, more subjects achieved HbA(1c)<7% and <= 6.5% in the BIAsp 30 BID group than in the exenatide group (HbA(1c)<7%: 37% vs. 20%, p = 0.0060; HbA(1c) <= 6.5%: 25% vs. 8%, p = 0.0004, respectively). Combined hypoglycemic episodes (major, minor, symptoms only) were reported by 56%, 61%, and 29% of the subjects in the BIAsp 30 QD, BIAsp 30 BID, and exenatide groups, respectively. Weight gain was observed in the BIAsp 30 group (BIAsp 30 QD: 2.85 kg, BIAsp 30 BID: 4.08 kg) and weight loss was observed in the exenatide group (- 1.96 kg). Nausea or vomiting was responsible for discontinuation of seven subjects in the exenatide group and one subject in the BIAsp 30 BID group. Conclusions: Significantly more T2DM patients (poorly controlled with combination metformin/sulfonylurea) achieved glycemic goals when treated with BIAsp 30 than with exenatide. The high baseline HbA1c values (similar to 10.2%) and the long duration of diabetes (similar to 9 years) suggests that some subjects may have been in an advanced stage of their diabetes and may not have had sufficient beta-cell function for a GLP-1 mimetic to be effective. The insulin-treated groups had more minor hypoglycemic events and weight gain but less gastrointestinal side-effects. In summary, BIAsp 30 was more efficacious in helping patients with high baseline HbA1c achieve glycemic goals. Clinical trial registration: www.clinicaltrials.gov, NCT00097877