Comparison of exenatide with biphasic insulin aspart 30 on glucose variability in type 2 diabetes: study protocol for a randomized controlled trial

Shaoyong Xu, Xiangyang Liu, Jie Ming, Qiuhe Ji, Shaoyong Xu, Xiangyang Liu, Jie Ming, Qiuhe Ji

Abstract

Background: Apart from the mean level of glycemic control, the extent of glucose excursions is another important issue to consider in type 2 diabetes mellitus (T2DM) management. Studies have showed that fluctuations of glucose seem to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as acute glucose swings activate the oxidative stress. However, until now, no randomized controlled trials have been conducted with the primary aim to evaluate glycemic fluctuation in the comparison between twice-daily exenatide and other treatment paradigms (for example, biphasic insulin aspart 30).

Methods/design: This multicenter, open-label, randomized, parallel trial includes a 1-week screening period and a 16-week treatment period. After the screening period, 150 patients with confirmed type 2 diabetes who are treated with stable, maximum-tolerated doses of metformin will be randomly assigned to one of two groups for antihyperglycemic therapies: exenatide and biphasic insulin aspart 30. The treatment with exenatide will be initiated at a low dose of 5 μg twice a day for 4 weeks and then titrated up to a standard dose of 10 ug twice a day until the completion of the study. The adjustment of insulin dose is instructed to achieve an optimal balance between glycemic control and the risk of hypoglycemia as dictated by clinical practice. The primary outcome is the absolute change of mean amplitude of glycemic excursion from baseline to week 16, which is calculated based on a real-time continuous glucose monitoring system (CGMS).

Discussion: This is the first randomized controlled trial using a CGMS to evaluate glycemic fluctuation between twice-daily exenatide and insulin aspart 30, which will provide beneficial evidence of exenatide usage in patients with T2DM.

Trial registration number: NCT02449603 . Date of registration: 11 May 2015.

References

    1. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362:1090–101. doi: 10.1056/NEJMoa0908292.
    1. Xu Y, Wang L, He J, Bi Y, Li M, Wang L, et al. Prevalence and control of diabetes in Chinese adults. JAMA. 2013;310:948–59. doi: 10.1001/jama.2013.168118.
    1. American Diabetes Association Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(Suppl 1):S14–80. doi: 10.2337/dc14-S014.
    1. Linong J, Bo Feng SQ. The safety and efficacy of initiating insulin therapy in Chinese patients with type 2 diabetes mellitus inadequately controlled with previous oral antidiabetic drugs. Chin J of Diabetes. 2011;19:746–51.
    1. Kvapil M, Swatko A, Hilberg C, Shestakova M. Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes. Diabetes Obes Metab. 2006;8:39–48. doi: 10.1111/j.1463-1326.2005.00492.x.
    1. Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept. 2004;117:77–88. doi: 10.1016/j.regpep.2003.10.028.
    1. Keating GM. Exenatide. Drugs. 2005;65:1681–92. doi: 10.2165/00003495-200565120-00008.
    1. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2628–35. doi: 10.2337/diacare.27.11.2628.
    1. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092–100. doi: 10.2337/diacare.28.5.1092.
    1. Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–91. doi: 10.2337/diacare.28.5.1083.
    1. Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006;8:436–47. doi: 10.1111/j.1463-1326.2006.00602.x.
    1. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005;143:559–69. doi: 10.7326/0003-4819-143-8-200510180-00006.
    1. Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57:1349–54. doi: 10.2337/db08-0063.
    1. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7. doi: 10.1001/jama.295.14.1681.
    1. Hanefeld M, Temelkova-Kurktschiev T. Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications. Nutr Metab Cardiovasc Dis. 2002;12:98–107.
    1. Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia. 2007;50:259–67. doi: 10.1007/s00125-006-0510-2.
    1. Irace C, Fiorentino R, Carallo C, Scavelli F, Gnasso A. Exenatide improves glycemic variability assessed by continuous glucose monitoring in subjects with type 2 diabetes. Diabetes Technol Ther. 2011;13:1261–3. doi: 10.1089/dia.2011.0096.
    1. Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970;19:644–55. doi: 10.2337/diab.19.9.644.
    1. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005;19:178–81. doi: 10.1016/j.jdiacomp.2004.10.001.
    1. Gallwitz B, Bohmer M, Segiet T, Molle A, Milek K, Becker B, et al. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011;34:604–6. doi: 10.2337/dc10-1900.

Source: PubMed

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