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.


METHODS
Subjects (N = 372, T2DM > 6 months, age > or = 18 and < or = 80 years, HbA1c > or = 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 microg BID for 4 weeks and 10 microg 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 HbA1c < 7% and < or = 6.5% in the BIAsp 30 BID group than in the exenatide group (HbA1c < 7%: 37% vs. 20%, p = 0.0060; HbA1c < or = 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 (approximately 10.2%) and the long duration of diabetes (approximately 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.


BACKGROUND
www.clinicaltrials.gov, NCT00097877.
Bergenstal
Richard
R
International Diabetes Center at Park Nicollet, Minneapolis, MN, USA.
Lewin
Andrew
A
Bailey
Timothy
T
Chang
Denise
D
Gylvin
Titus
T
Roberts
Victor
V
D000328:Adult; D061265:Biphasic Insulins; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D061265:Biphasic Insulins; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms; C557564:insulin aspart, insulin aspart protamine drug combination 30:70; D007336:Insulin, Isophane; D008687:Metformin; D000077270:Exenatide; D061267:Insulin Aspart