Evaluation of the efficacy and safety of lixisenatide add-on treatment to basal insulin therapy among T2DM patients with different body mass indices from GetGoal trials

Diabetology & Metabolic Syndrome

Yutaka Seino²  Yusuke Naito³  Kazuhiro Eto¹ 

[1] Department of Internal Medicine, School of Medicine, Teikyo University, Tokyo, Japan;Kansai Electric Power Hospital, Osaka, Japan;Sanofi K.K., Tokyo, Japan

关键词: Type 2 diabetes mellitus;    Lixisenatide;    Body mass index;   

Others  :  1234349
DOI  :  10.1186/s13098-015-0104-6

 received in 2015-06-11, accepted in 2015-11-09,  发布年份 2015

【 摘 要 】

Background

Using patient data from the GetGoal-Duo1, -L, and L-Asia trials, the objectives of this study were to evaluate and compare the impact of lixisenatide once-daily add-on treatment to basal insulin therapy ±oral antidiabetic drugs (OADs) among type 2 diabetes (T2DM) patients subdivided into groups, based on their baseline body mass indices (BMI).

Methods

Data of patients treated with lixisenatide were extracted from the modified intent-to-treat populations of the trials. Patients were subdivided into 4 groups based on baseline BMI category (BMIs <25, 25–<30, 30–<35, and ≥35 kg/m ² ). At the unadjusted data level, efficacy and safety endpoints were evaluated and compared among study cohorts. Additionally, multivariable regression analyses were used to specify key patient characteristics and then assess the adjusted outcomes.

Results

Of the 662 T2DM patients, the mean changes in HbA1c (−0.63 to −0.73 %, p = 0.88) and FPG levels (−3.9 to 3.2 mg/dL, p = 0.60) were not significantly different among the different BMI groups. The proportions of T2DM patients that achieved HbA1c <7 % ranged between 34.7 and 46.8 %. After adjusted for patient characteristics, T2DM patients in the lowest BMI group relative to those in the highest BMI group had a smaller reduction in HbA1c during the trial periods (difference: 0.32 %, confidence interval: 0.10, 0.53, p = 0.005) and were less likely to achieve HbA1c <7 %.

Conclusions

The findings of this analysis of the GetGoal clinical trials suggest that lixisenatide may be a good treatment option for optimizing glycemic control in patients unable to achieve their HbA1c target on basal insulin therapy ±OADs, regardless of BMI category.

【 授权许可】

   
2015 Eto et al.

【 图 表 】

Fig.1.

【 参考文献 】

• [1]Riddle MC, Rosenstock J, Gerick J: Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003, 26:3080-3086.
• [2]Aronson R: Optimizing glycemic control: lixisenatide and basal insulin in combination therapy for the treatment of Type 2 diabetes mellitus. Expert Rev Clin Pharmacol. 2013, 6:603-612.
• [3]Raccah D, Bretzel RG, Owens D, Riddle M: When basal insulin therapy in type 2 diabetes mellitus is not enough–what next? Diabetes Metab Res Rev. 2007, 23:257-264.
• [4]Woerle HJ, Neumann C, Zschau S, Tenner S, Irsigler A, Schirra J, et al.: Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes. Importance of postprandial glycemia to achieve target HbA 1c levels. Diabetes Res Clin Pract 2007, 77:280-285.
• [5]Riddle MC, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Silvestre L, et al.: Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). Diabetes Care 2013, 36:2497-2503.
• [6]Riddle MC, Aronson R, Home P, Marre M, Niemoeller E, Miossec P, et al.: Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care 2013, 36:2489-2496.
• [7]Seino Y, Min KW, Niemoeller E: Takami A; EFC10887 GETGOAL-L Asia Study Investigators. Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diabetes Obes Metab 2012, 14:910-917.
• [8]Bays HE, Chapman RH, Grandy S: SHIELD Investigators’ Group: The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys. Int J Clin Pract 2007, 61:737-747.
• [9]WHO Expert Consultation: Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies Lancet 2004, 363:157-163.
• [10]Woerle HJ, Neumann C, Zschau S, Irsigler A, Schirra J, Gerich JE, et al.: Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes. Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract 2007, 77:280-285.
• [11]Monnier L, Lapinski H, Colette C: Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care 2003, 26:881-885.
• [12]Riddle M, Umpierrez G, DiGenio A, Zhou R, Rosenstock J: Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes. Diabetes Care 2011, 34:2508-2514.
• [13]Riddle M, Seino Y, Cariou B, Huelgas RG, Roy-Duval C, Hecquet C, et al. Once-daily lixisenatide as add-on to basal insulin ± OADs in patients with type 2 diabetes selectively reduces postprandial hyperglycemic daytime exposure. Poster presentation at 73rd American Diabetes Association Scientific Sessions. June 21–25, 2013. Chicago.
• [14]Bonora E: Postprandial peaks as a risk factor for cardiovascular disease: epidemiological perspectives. Int J Clin Pract Suppl. 2002, 129:5-11.
• [15]Gerich J: Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies. Int J Gen Med 2013, 6:877-895.
• [16]Ceriello A, Hanefeld M, Leiter L, Monnier L, Moses A, Owens D, et al.: Postprandial glucose regulation and diabetic complications. Arch Intern Med 2004, 164:2090-2095.
• [17]International Diabetes Federation IDF guidelines for management of postmeal glucose in patients with diabetes. http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf. Accessed 19 Mar 2014.
• [18]Clinicaltrials.gov. Evaluation of Cardiovascular Outcomes in Patients with Type 2 Diabetes after Acute Coronary Syndrome During Treatment with AVE0010 [Lixisenatide], NCT01147250. http://clinicaltrials.gov/ct2/show/NCT01147250?term=NCT01147250&rank=1. Accessed 19 Mar 2014.
• [19]Rubin DJ, Rybin D, Doros G, McDonnell ME: Weight-based, insulin dose-related hypoglycemia in hospitalized patients with diabetes. Diabetes Care 2011, 34:1723-1728.