Diabetes Management
Table 3: Head-to-head Clinical Trial Data for Incretin-based Therapies Treatment
Effect of Treatment on: HbA1c
Liraglutide 1.8 mg qd Liraglutide reduced mean
(-1.12 % [SE 0.08] versus -0.79 % [SE 0.08]; p<0.0001)
FPG Liraglutide lowered mean
versus exenatide 10 µg bid HbA1c more than exenatide FPG more than exenatide for 26 weeks
(-28.98 mg/dl [SE 0.20] Body Weight
Both led to similar weight loss (-3.24 kg with
liraglutide versus -2.87 kg
versus -10.80 mg/dl [SE 0.20]; with exenatide) p<0.0001)
Both well tolerated, but less
persistent nausea with liraglutide (estimated treatment rate ratio 0.448, p<0.0001) and only minor
Test switching from exenatide 10 µg bid to liraglutide 1.8 mg qd or remaining on liraglutide qd for 26 weeks
Exenatide 5 µg bid then 10 µg bid versus sitagliptin 100 mg qam for two weeks Liraglutide 1.2 mg or 1.8 mg qd versus
sitagliptin 100 mg qd for 26 weeks
Participants continued the
versus sitaliptin 100 mg qd in a 26-week extension
Switch to liraglutide further reduced HbA1c (-0.32 %,
p<0.0001) NA
Switch to liraglutide further reduced FPG (-16.2 mg/dl, p<0.0001)
Switch to liraglutide further reduced body weight (-0.9 kg, p<0.0001)
hypoglycemia (1.93 versus 2.60 events for liraglutide and exenatide, repectively, per patient per year, p=0.0131)53 Switch to liraglutide well tolerated, with minor hypoglycemia (1.30 episodes per patient per year) or nausea (3.2 %) versus 1.5 % in those continuing liraglutide54
Reduction similar with both Exenatide reduced body weight Mild to moderate gastrointestinal treatments (-15 mg/dl versus more than sitagliptin (-0.8 kg adverse events with both -19 mg/dl)
versus -0.3 kg, p=0.0056)
Liraglutide lowered HbA1c more Mean decreases greater with Weight loss greater with than sitagliptin (-1.24 % and
-1.50 %, respectively, versus -0.90 %, both p<0.0001)
treatments64 Nausea more common with
both doses of liraglutide than both doses of liraglutide than liraglutide, similar frequency with sitagliptin (-33.66 mg/dl with sitagliptin (-2.86 kg and of minor hypoglycemia for and -38.52 mg/dl, respectively, versus
-3.38 kg, respectively, versus all groups66 -0.96 kg, p<0.0001)
-14.94 mg/dl, both p<0.0001)
above treatment of liraglutide than sitagliptin (-1.29 % and 1.2 mg or 1.8 mg qd
Liraglutide lowered HbA1c more Mean decreases greater with Weight loss greater with both doses of liraglutide
-1.51 % versus -0.88 %, both than with sitagliptin p<0.0001)
Minor hypoglycemia (8.1 %, 8.3 %,
(-30.78 mg/dl and -36.72 mg/dl versus -1.16 kg, p<0.0001) versus -10.62 mg/dl, both p<0.0001)
Exenatide 2 mg qw versus
liraglutide 1.8 mg qd
Liraglutide lowered HbA1c more than exenatide qw
(-1.48 % [SE 0.05] versus -1.28 % [SE 0.05])
NA
Weight loss greater with liraglutide than with exenatide qw
(-3.58 kg versus -2.68 kg)
liraglutide than with sitagliptin and 6.4 % with liraglutide 1.2 mg, (-2.78 kg and -3.68 kg versus liraglutide 1.8 mg, and sitagliptin, respectively). Gastrointestinal side effects (including nausea)
more frequently seen with liraglutide, declined after several weeks85
Minor hypoglycemia (10.8 % and 8.9 % with exenatide qw and liraglutide, respectively).
Gastrointestinal side effects and withdrawal due to adverse events lower with exenatide qw67
AE = adverse event; Bid = twice daily; FPG = fasting plasma glucose; HbA1c = glycosylated hemoglobin; NA = not available; qam = every morning; qd = once daily; qw = once weekly; SE = standard error.
Other studies have compared liraglutide directly with exenatide twice daily, and liraglutide directly with sitagliptin.53,54,62,63,66
A 26-week extension study revealed sustained efficacy of liraglutide The LEAD-6 trial (n=464)
reported superior results for liraglutide over exenatide twice daily in HbA1c reduction (-1.12 % versus -0.79 %, respectively; p<0.0001). The patients
treated with liraglutide also reported significantly higher overall treatment satisfaction compared with the exenatide group (p=0004). Patients who switched from exenatide twice daily to liraglutide in the 14-week extension
phase gained further improvements in HbA1c. Mean A1C further decreased from 7.2 % at Week 26 to 6.9 % at Week 40 (p<0.0001) after switching from exenatide to liraglutide, but remained similar with continued liraglutide (7.0 % to 6.9 %; p=0.1222). Figure 2 illustrates some of the therapeutic benefits of switching from exenatide twice daily to liraglutide in this study.54
Liraglutide 1.8 mg or 1.2 mg was linked with decreases of 1.50 % and
1.24 % in HbA1c levels, respectively, from baseline in a 26-week trial of 665 metformin-treated patients, compared with a 0.90 % reduction with sitagliptin 100 mg (both liraglutide doses p<0.0001 versus sitagliptin).
88
versus sitagliptin, with significantly greater HbA1c reductions from baseline at 52 weeks. Estimated mean treatment differences after one year were -0.40 % and -0.63 % with liraglutide 1.2 mg and 1.8 mg, respectively, versus sitagliptin (p<0.0001 for both comparisons). Adding 1.8 mg liraglutide to metformin increased overall treatment satisfaction scores, which were significantly higher in the liraglutide groups than in the sitagliptin group (4.35 versus 2.96 point increase with liraglutide versus sitagliptin, respectively, p=0.03), and this difference was maintained at 52 weeks (4.3 versus 3.0 point increase, respectively, p=0.03).66
In the trial to compare the efficacy and safety of exenatide once weekly versus liraglutide in patients with type 2 diabetes (DURATION-6), both treatment groups showed robust glycemic lowering with related weight
loss. Reductions in HbA1c and weight loss were greater with daily liraglutide injections, while gastrointestinal (GI) side effects and withdrawals due to adverse events were significantly lower with exenatide once weekly.67
US ENDOCRINOLOGY Adverse Effects and Reference
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