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

Curr Med Res Opin. 2009 Jan;25(1):65-75. doi: 10.1185/03007990802597951.

Abstract

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: 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.

Clinical trial registration: www.clinicaltrials.gov, NCT00097877.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biphasic Insulins
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Exenatide
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use
  • Insulin Aspart
  • Insulin, Isophane
  • Male
  • Metformin / administration & dosage
  • Metformin / therapeutic use*
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use*
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / therapeutic use*
  • Venoms / administration & dosage
  • Venoms / adverse effects
  • Venoms / therapeutic use*

Substances

  • Biphasic Insulins
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • Sulfonylurea Compounds
  • Venoms
  • insulin aspart, insulin aspart protamine drug combination 30:70
  • Insulin, Isophane
  • Metformin
  • Exenatide
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT00097877