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

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 ≥ 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 µg BID for 4 weeks and 10 µg BID thereafter). Efficacy (HbA_1c, 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 HbA_1c values (∼10.2%) and the long duration of diabetes (∼9 years) suggests that some subjects may have been in an advanced stage of their diabetes and may not have had sufficient β-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 HbA_1c achieve glycemic goals.

Clinical trial registration: www.clinicaltrials.gov, NCT00097877

Key words: :

• BIAsp 30
• GLP-1
• Incretin mimetic
• Type 2 diabetes

Acknowledgements

Declaration of interest: This study was supported by Novo Nordisk Inc. The authors thank the patients, investigators, and their staff for participating in the study. R. B. has participated in clinical research and scientific advisory boards for Eli Lilly, Novo Nordisk and Sanofi-Aventis. He receives no personal compensation for any of these activities. T. B. received grant support from Novo Nordisk, Eli Lilly, and Amylin. He is on the speaker's bureau for Novo Nordisk, Eli Lilly, and Amylin. A. L. has participated or is currently participating in clinical trials for 7TM Pharma, Abbott Laboratories, ActivX Biosciences, Inc., Amylin Pharmaceuticals, AstraZeneca, and many other companies. D. C. and T. G. are employees of Novo Nordisk Inc. V. R. has received financial support in the form of clinical research grants, consulting and speaking fees from: Novo Nordisk, Eli Lilly, Sanofi-Aventis, Pfizer, Merck, GlaxoSmithKline, Medtronic-Minimed, BMS, Novartis, Takeda, and Amylin. The authors thank Madhu Mawal-Dewan, Novo Nordisk, for assistance with the development of the manuscript.

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

The BIAsp-1714 NovoLog Mix-vs.-Exenatide Study Group includes J Adler, J Agaiby, N Aquino, P Arcuri, N Askari, T Bailey, A Barajas, A Bartkowiak, R Baumbach, G Bedel, A Behnke, R Blank, B Bode, O Brusco, J Burbano, R Burton, E Busick, C Chappel, C Corder, W Cox, N Daboul, W DeBell, R Desai, J Doris, R Elijah, E Eskander, J Evans, J Fidelholtz, M Gaines, K Ganong, G Gollapudi, G Gottschlich, R Graf, A Haider, I Hartman, B Henson, J Hoesktra, Y-L Hsu, R Hunter, W Jacks, R Jain, P James, A Jimenez, S Johns, D Johnson, G Journeay, J Kaladas, G Kiel, C Kistler Jr., Y Khronusova, L Koehler, Y Kurtzer, S Landgarten, P Levin, A Lewin, L Levinson, M Lindley, T. Littlejohn, J Lock, I Marar, K Longshaw, K Lucas, M Magee, L Maletz, E Maybach, J McNeff, A Mercado, B Mizock, C Newton, M Nida, R Nurnberg, M Olken, S Ong, E Osea, I Oudeh, B Patel, A Pathak, J Pollock, C Powers, R Prabhu, A Pragalos, J Quesada, A Radparvar, M Raikhel, P Raskin, J Reed, V Roberts, M Robinson, M Schear, S Schwartz, B Seidman, J Castro-Skoglund, R Stout, D Streja, R Strzinek, D Sugimoto, R Tamayo, S Touger, J Turner, J Turns, J Vogt, H Waldo, G Walker, M Warren, P Weissman, J Wood, D Yarrish, and S Yates.