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Lixisenatide – Once-daily Glucagon-like Peptide-1 Receptor Agonist in the Management of Type 2 Diabetes post-prandial blood glucose levels following a standardised


breakfast, as well as mean plasma glucose and HbA1C levels, were significantly reduced in both the once-daily and twice-daily lixisenatide 20 µg groups compared with placebo.25


At the time of writing, the results of some of these trials have been made available as press releases, or have been presented at scientific meetings and published in abstract form. Table 2 shows a summary of the clinical trial programme.


GetGoal-Mono GetGoal-Mono was a 12-week, double-blind, randomised controlled trial that assessed the efficacy and safety of lixisenatide as monotherapy for type 2 diabetes.27


A total of 361 type 2 diabetes


patients not on any diabetes medication were randomised to one of four groups: lixisenatide two-step titration (10 µg once daily for one week, followed by 15 µg once daily for one week, and 20 µg once daily thereafter; n=120), lixisenatide one-step titration (10 µg once daily for two weeks, and 20 µg once daily thereafter; n=119), placebo two-step titration (n=61), or placebo one-step titration (n=61). Patients had a


mean age of 54 years, mean disease duration of 2.5 years, and HbA1C in the range 7–10 %.


In the lixisenatide groups, HbA1C decreased significantly (p<0.0001) by comparison with placebo (lixisenatide two-step group -0.73 ± 0.12 %;


lixisenatide one-step group -0.85 ± 0.12 %; placebo -0.19 ± 0.12 %). At the end of the study, the lixisenatide groups included significantly


more patients with HbA1C ≤6.5% (lixisenatide two-step group 31.9 %; lixisenatide one-step group 25.4 %; placebo 12.5 %) and HbA1C <7.0 % (lixisenatide two-step group 52.2 %; lixisenatide one-step group


46.516 %; placebo 26.816 %). They also had significantly higher reductions in two-hour post-prandial glucose levels (lixisenatide two-step group -81.18 ± 4.56 mg/dl; lixisenatide one-step group - 98.46 ± 9.9 mg/dl; placebo -11.7 ± 10.08 mg/dl) and fasting plasma glucose levels (lixisenatide two-step group -12.24 ± 4.5 mg/dl; lixisenatide one-step group -16.02 ± 4.5 mg/dl; placebo 3.42 ± 4.68 mg/dl).27


GetGoal-L-Asia GetGoal-L-Asia was a 24-week multicenter, randomised, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of lixisenatide 20 µg once daily in 311 patients with type 2 diabetes (mean age 58 years, disease duration 14 years, and BMI 25 kg/m2) from Japan, South Korea, Taiwan and the Philippines who were inadequately controlled with basal insulin and/or a sulfonylurea.28


At week 24, lixisenatide had significantly reduced mean HbA1C levels from baseline (-0.77 ± 0.137 %) compared with placebo (0.11 ±


0.131 %; least squares [LS] mean difference -0.88 [95 % CI -1.116 to 0.650]). The percentages of patients on lixisenatide who achieved


EUROPEAN ENDOCRINOLOGY


Phase III Clinical Trial Programme The GetGoal clinical trial programme initially consisted of nine Phase III trials evaluating the efficacy and safety of lixisenatide in the treatment of patients with type 2 diabetes as monotherapy or in combination with different oral antidiabetes agents and/or insulin. Additional studies have been added to the GetGoal clinical programme, including randomised studies comparing lixisenatide to sitagliptin and a large clinical trial evaluating cardiovascular outcomes with lixisenatide in a type 2 diabetes patient who had had a recent acute coronary syndrome. The trials began in May 2008 and 4,300 patients have been enrolled in total.26


Table 3: Additional Results for Lixisenatide versus Placebo from the GetGoal-L-Asia Study28


Lixisenatide Placebo


LS Mean Difference (95 % CI)


Two-hour post-prandial -143.28 ± 10.73 -2.52 ± 10.49 -140.94 glucose levels (mg/dl) Glucose excursion (mg/dl)


-127.62 ± 10.37 2.52 ± 9.76


Average 7-point self-monitoring of


plasma glucose (mg/dl)


CI = confidence interval; LS = least squares.


HbA1C <6.5 % and <7 % were 17.8 % and 35.6 %, respectively, compared with 1.3 % and 5.2 %, respectively, in the placebo group


(p<0.0001).28 Other measures of efficacy also were significantly improved (see Table 3).28


GetGoal-X GetGoal-X compared lixisenatide to exenatide in a 24-week multicentre, randomised, open-label, parallel-group study of 634 type 2 diabetes patients insufficiently controlled on metformin.29 The patients had a mean age of 57.4 years, a disease duration of


6.8 years, a BMI of 33.6 kg/m2, and HbA1C levels of 8 %. The decrease in HbA1C with lixisenatide (-0.79 ± 0.05 %) was comparable with that seen with exenatide (-0.96 ± 0.05 %; LS mean difference 0.17 [95 % CI


0.03–0.30]; p=0.17). Similar percentages of patients achieved HbA1C <7 % with lixisenatide (48.5 %) and with exenatide (49.8 %). The mean


decrease in body weight was comparable between the lixisenatide and exenatide groups.29


GetGoal-S GetGoal-S, a 24-week randomised, double-blind, placebo-controlled clinical study, evaluated the efficacy and safety of lixisenatide in type 2 diabetes patients insufficiently controlled on sulfonylurea and/or metformin. In the study, 859 patients were randomised to either lixisenatide or placebo.30


Doses were increased in a step-wise manner to 20 µg once daily in both groups. As an add-on therapy to sulfonylurea with or without metformin,


lixisenatide significantly reduced HbA1C levels and improved two-hour post-prandial glucose and fasting plasma glucose levels compared with placebo.30


experienced a significant decrease in body weight compared with those on placebo.30


At 24 weeks, lixisenatide significantly reduced


HbA1C compared with placebo (-0.85 versus -0.10%; p<0.0001). Lixisenatide also significantly improved two-hour PPG (after a


standardised meal test) (-6.19 versus -0.21 mmol/l), FPG (-0.99 versus -0.36 mmol/l), and body weight (-1.76 versus -0.93 kg) and


increased the proportion of patients achieving HbA1C <7.0 % (36.4 versus 13.5 %) (p<0.0001). GetGoal-L


GetGoal-L is another 24-week clinical study in which 495 patients were randomised either to lixisenatide or placebo in addition to basal insulin with or without metformin. Compared with placebo,


lixisenatide significantly decreased mean HbA1C (p=0.0002), improved post-prandial glucose following a standardised meal (p<0.0001) and reduced mean body weight (p<0.0001).


15 Moreover, patients on lixisenatide 34.38 ± 4.90 10.08 ± 4.88 -24.3 (-33.174 to -15.498)


(-159.966 to -121.842) -129.96


(-148.41 to -111.672)


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