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Diabetes Management


Table 2: Overview of Phase III Clinical Trials of Lixisenatide Study Description


GetGoal-Mono


Efficacy and safety of lixisenatide as monotherapy in patients with type 2 diabetes27 GetGoal-L-Asia


Efficacy and safety of lixisenatide as add-on to basal insulin with or without sulfonylurea versus placebo28 GetGoal-X


Effect of lixisenatide versus exenatide on


glycemic control in patients with type 2 diabetes insufficiently controlled on metformin29 GetGoal-S


Effect on glycaemic control of lixisenatide as add-on to sulfonylurea with or without metformin versus placebo30 GetGoal-L


Efficacy and safety of lixisenatide as add-on to basal insulin with or without metformin versus placebo26 GetGoal-M


Effect on glycaemic control of lixisenatide (morning versus evening dose) as add-on to metformin compared with placebo51 GetGoal-F1


Effect on glycaemic control of lixisenatide in two titration


regimens as add-on to metformin versus placebo52 GetGoal-P


Glycaemic control of lixisenatide as add-on to pioglitazone versus placebo GetGoal-Mono-Japan


Efficacy and safety of lixisenatide as monotherapy in patients with type 2 diabetes Lixisenatide versus sitagliptin as add-on to metformin


in patients with type 2 diabetes, evaluating effects on glycaemic control and body weight in 24 weeks Lixisenatide as add-on to metformin and insulin glargine in patients with type 2 diabetes compared with placebo, evaluating effects on glycaemic control in 24 weeks53 ELIXA


Evaluate cardiovascular outcomes of lixisenatide in patients with type 2 diabetes who had a recent acute coronary syndrome compared with placebo GetGoal-M-As


Efficacy of lixisenatide as add-on to metformin with or


without sulfonylurea versus placebo in reducing HbA1C in a period of 24 weeks


2hr-PPG = two-hour post-prandial glucose; FPG = fasting plasma glucose; HbA1C = glycosylated haemoglobin; SMPG = self-monitoring of plasma glucose.


plasma glucose and two-hour post-prandial plasma glucose following a standardised breakfast. By the end of the study (week 13),


significantly higher proportions of patients achieved HbA1C <7 % in lixisenatide groups (47–69 % in once-daily and 51–77 % in twice-daily groups) compared with the placebo group (32 %). A dose-dependent reduction in body weight was seen in lixisenatide-treated patients, which was significant in the 20 µg once daily (-3.01 ± 0.41 kg), 30 µg once daily (-3.47 ± 0.41 kg) and 30 µg twice daily (-3.89 ± 0.41 kg) groups compared with placebo (-1.94 ± 0.32 kg).24


Significant


reductions in fasting plasma glucose were observed in the 30 µg once daily (-23.76 ± 4.50 mg/dl), 10 µg twice daily (-17.64 ± 4.32 mg/dl), 20 µg twice daily (-20.34 ± 4.50 mg/dl) and 30 µg twice daily (-25.56 ± 4.50 mg/dl) groups compared with placebo (-3.78 ± 3.42 mg/dl).24


Mean


two-hour post-prandial glucose concentrations in all lixisenatide groups showed a significant reduction by comparison with placebo.24


14


The study indicated that efficacy was similar between the once- and twice-daily regimens and that there was a dose–response relationship. A dose of 20 µg lixisenatide once daily demonstrated the best efficacy:tolerability ratio. The data suggest further increases in the dose may not provide added benefit.


In a Phase II randomised, double-blind, placebo-controlled study involving 64 patients, lixisenatide once or twice daily was added to metformin and/or a sulfonylurea for 28 days. The study measured the effects of lixisenatide on post-prandial change in blood glucose following a standardised breakfast and on levels of fasting and mean


plasma glucose and HbA1C. It also evaluated the safety and tolerability of the drug.25


The lixisenatide dose started at 5 µg


subcutaneous once daily or twice daily and was increased by 2.5 µg every five days to a maximum dose of 20 µg. On day 28,


EUROPEAN ENDOCRINOLOGY NCT0076381546 450 NCT0090525547 66 NCT0097693748 ~300 NCT0097528649 ~450 NCT0114725050 ~6,000 June 2011 January 2011 April 2011 NCT0071383041 859 NCT0071562442 495 NCT0071267343 680 NCT0076345145 450


Trial Registration No. No. Subjects Completion Date Results NCT0068870138


361 NCT0086665839 311


December 2009 Significant decrease in HbA1C, 2hr-PPG, and FPG; significant number of patients


June 2010


achieving HbA1C <7 % and <6.5 % Significant decrease in HbA1C, 2hr-PPG,


glucose excursion, average 7-point SMPG; significant number of patients achieving


HbA1C <7 % and <6.5 % NCT0070703140 634


November 2010 Lixisenatide had similar HbA1C lowering and weight loss effects as exenatide


January 2011 February 2011 March 2011 January 2011 Significant reduction in HbA1C,


improvement in 2hr-PPG and FPG, and decrease in body weight


Significant reduction in HbA1C,


improvement in PPG, and decrease in body weight


Both morning and evening lixisenatide dosing improved glycaemic control when added to metformin


Both 1-step and 2-step titration regimens were effective and well-tolerated


Not available Not available Not available


September 2011 The combination of basal insulin and lixisenatide reduced HbA1c and


significantly improved 2hr-PPG October 2013 Ongoing study


NCT0116977944


~380


December 2011 Ongoing study


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