Exenatide antidiabetic drugs

Description Results NMA

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

exenatide (10 ìg twice daily) administered subcutaneously before lunch and dinner (n=187)

vs.

exenatide (10 ìg twice daily) administered subcutaneously before breakfast and dinner (n=190)

open

Parallel groups

Sample size: 187/190

Primary endpoint:

FU duration:

phase 3b

exenatide once monthly at a low, medium or high dose, each administered once every four weeks, for a total of 20 weeks (n=121)

vs.

exenatide 2mg once weekly (n=0)

open

Parallel groups

Sample size: 121/0

Primary endpoint:

FU duration: 20 weeks

phase 2

10 mug exenatide administered twice a day (n=-9)

vs.

long-acting release formulation of exenatide 2 mg administered once weekly (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 30 weeks

exenatide twice daily 5 et 10 µg for 24 weeks (n=-9)

vs.

placebo (n=78)

3 arms: exenatide 5µg BID, 10µg bid, placebo

double-blind

Parallel groups

Sample size: -9/78

Primary endpoint: change in HbA1c

FU duration: 24 weeks

exenatide twice-daily (n=111)

vs.

placebo (n=54)

Sample size: 111/54

Primary endpoint:

FU duration:

nausea 4.99 [2.66; 9.34]

vomiting 4.45 [1.76; 11.27]

diarrhoea 2.23 [1.11; 4.45]

death 0.00 [0.00; NaN]

severe hypoglycemia 0.00 [0.00; NaN]

treatment-emergent adverse events (TEAEs) 1.13 [0.98; 1.30]

severe adverse events 0.65 [0.27; 1.56]

twice-daily 10 µg exenatide injections (n=138)

vs.

placebo (on top insulin glargine) (n=123)

double-blind

Parallel groups

Sample size: 138/123

Primary endpoint: change in HbA1c

FU duration: 30 weeks

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

CV events 0.91 [0.83; 1.00] Demonstrated

all causes death 0.86 [0.77; 0.97]

CVdeath 0.88 [0.76; 1.02]

fatal and non fatal stroke 0.85 [0.70; 1.03]

fatal and non fatal MI 0.97 [0.85; 1.10]

Hospitalization for heart failure 0.94 [0.78; 1.13]

10 microg exenatide twice daily injection + lifestyle modification program (n=96)

vs.

placebo + lifestyle modification program (n=98)

double-blind

Parallel groups

Sample size: 96/98

Primary endpoint:

FU duration: 24 weeks

subcutaneous injections of extended-release exenatide at a dose of 2 mg once weakly (n=7356)

vs.

placebo (n=7396)

double-blind

Parallel groups

Sample size: 7356/7396

Primary endpoint: CV death, MI, stroke

FU duration: 3.2 years median

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

nausea ∞ [NaN; ∞]

vomiting ∞ [NaN; ∞]

diarrhoea ∞ [NaN; ∞]

severe hypoglycemia NaN [NaN; NaN]

ant hypoglycemia 3.52 [0.44; 28.13]

Exenatide 10–20 µg daily (n=155)

vs.

Placebo (n=78)

double blind

Parallel groups

Sample size: 155/78

Primary endpoint:

FU duration: 24 weeks

exenatide for 28 days (n=99)

vs.

placebo (n=0)

Subjects were randomly assigned to one of six treatment groups (A1, A2, A3, B, C, or D). Subjects assigned to exenatide groups B, C, and D received 10 ìg twice daily (BID) (group B), 10 ìg once daily (QD) (group C), or 20 ìg QD (group D) during the 4-week, triple-blind treatment period. Subjects assigned to placebo groups A1, A2, and A3 received placebo BID (A1) or QD (A2, A3) in dose volumes equivalent to those received by groups B, C, and D, respectively.

double-blind

Sample size: 99/0

Primary endpoint: HbA1c change

FU duration: 28 days

phase 2

exenatide at 2.5, 5.0, 7.5, or 10.0 microg administered b.i.d. for 28 days (n=-9)

vs.

placebo (n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint: not defined

FU duration: 28 days

dose-ranging study

exenatide twice daily 10 µg for 24 weeks (n=78)

vs.

placebo (n=78)

3 arms: exenatide 5µg BID, 10µg bid, placebo

double-blind

Parallel groups

Sample size: 78/78

Primary endpoint: change in HbA1c

FU duration: 24 weeks

nausea 3.88 [1.01; 14.86]

death NaN [NaN; NaN]

CV events ∞ [NaN; ∞]

vomiting 3.88 [0.53; 28.41]

diarrhoea ∞ [NaN; ∞]

severe hypoglycemia ∞ [NaN; ∞]

ant hypoglycemia 1.05 [0.49; 2.25]

treatment-emergent adverse events (TEAEs) 1.40 [0.88; 2.23]

nausea 82.34 [11.55; 586.81]

vomiting 4.66 [2.22; 9.78]

diarrhoea 4.71 [1.82; 12.14]

treatment-emergent adverse events (TEAEs) 1.43 [1.23; 1.65]

death 1.96 [0.18; 21.48]

CV deaths 0.98 [0.06; 15.59]

CV events 1.96 [0.68; 5.65]

severe hypoglycemia NaN [NaN; NaN]

serious adverse events 1.69 [0.82; 3.48]

nausea 6.63 [4.43; 9.92]

vomiting 4.64 [2.40; 8.97]

diarrhoea 2.84 [1.30; 6.21]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events 1.58 [0.38; 6.54]

severe hypoglycemia 0.95 [0.24; 3.75]

nausea 1.58 [1.04; 2.40]

vomiting 3.08 [1.03; 9.27]

death NaN [NaN; NaN]

diarrhoea 1.48 [0.66; 3.33]

severe hypoglycemia NaN [NaN; NaN]

nausea 2.61 [1.60; 4.27]

vomiting 14.81 [2.00; 109.86]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

diarrhoea 2.16 [0.57; 8.15]

ant hypoglycemia 1.50 [0.65; 3.49]

nausea 5.36 [2.75; 10.43]

vomiting 3.94 [1.14; 13.61]

diarrhoea 2.76 [1.02; 7.42]

death NaN [NaN; NaN]

severe hypoglycemia NaN [NaN; NaN]

nausea 2.35 [1.78; 3.10]

vomiting 3.07 [1.59; 5.94]

diarrhoea 2.69 [1.56; 4.65]

ant hypoglycemia 3.77 [2.64; 5.38]

death 0.00 [0.00; NaN]

severe hypoglycemia ∞ [NaN; ∞]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

nausea ∞ [NaN; ∞]

severe hypoglycemia NaN [NaN; NaN]

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

nausea 3.50 [0.47; 25.90]

vomiting NaN [NaN; NaN]

severe hypoglycemia NaN [NaN; NaN]

ant hypoglycemia ∞ [NaN; ∞]

nausea 29.25 [7.23; 118.31]

ant hypoglycemia 3.92 [2.52; 6.10]

treatment-emergent adverse events (TEAEs) 1.58 [1.29; 1.94]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events 0.00 [0.00; NaN]

vomiting ∞ [NaN; ∞]

diarrhoea 1.49 [0.54; 4.11]

severe hypoglycemia 1.98 [0.18; 21.72]

nausea 1.90 [1.42; 2.54]

vomiting 3.30 [1.72; 6.33]

diarrhoea 1.58 [0.86; 2.88]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

Exenatide 20 µg daily (n=33)

vs.

Insulin on-top of sulphonylureas/metformin (n=16)

open

Parallel groups

Sample size: 33/16

Primary endpoint: glycemic control

FU duration: 16 weeks

Exenatide 20 µg daily (n=253)

vs.

Insulin on-top of sulphonylureas+metformin (n=248)

open

Parallel groups

Sample size: 253/248

Primary endpoint: HbA1c

FU duration: 52 weeks

Exenatide 20 µg daily (n=282)

vs.

Insulin on-top of sulphonylureas+metformin (n=267)

open

Sample size: 282/267

Primary endpoint:

FU duration: 26 weeks

Exenatide 10–20 µg daily (n=110)

vs.

Placebo on-top of Metformin (n=113)

3 arms : exenatide 5µg twice daily, 10µg twice daily and placebo

double blind

Parallel groups

Sample size: 110/113

Primary endpoint: HbA1c

FU duration: 30 weeks

Exenatide 20 µg daily (n=121)

vs.

Placebo on-top of thiazolidinediones+/-metformin (n=112)

double blind

Sample size: 121/112

Primary endpoint:

FU duration: 16 weeks

Exenatide 5µg twice daily (n=125)

vs.

Placebo on-top of SU (n=123)

3rd arms with exenatide 10µg BID

double blind (not adequate)

Parallel groups

Sample size: 125/123

Primary endpoint: HbA1c

FU duration: 30 weeks

Exenatide 10 µg bid (n=241)

vs.

Placebo on-top of sulphonylureas+metformin (n=247)

3 arms: exenatide 5, 10µg bid or placebo

double blind

Parallel groups

Sample size: 241/247

Primary endpoint: change in HbA1c

FU duration: 30 weeks

Exenatide 10µg daily for 12 weeks (n=111)

vs.

Placebo on-top of sulphonylureas +/-metformin/thiazolidinediones (n=40)

Exenatide 5–10–20 µg daily for 12 weeks

open

Parallel groups

Sample size: 111/40

Primary endpoint: change in HbA1c

FU duration: 12 weeks

exenatide LAR 0.8 or 2 µg daily (n=30)

vs.

Placebo on-top of metformin (n=15)

double blind

Parallel groups

Sample size: 30/15

Primary endpoint: not defined

FU duration: 15 weeks

exenatide 3 regimen (0.08 micro g/kg) for 28 days (n=109)

vs.

placebo (n=0)

4 arms: three subcutaneously injected regimens of AC2993 or placebo

double-blind

Parallel groups

Sample size: 109/0

Primary endpoint: not defined

FU duration: 28 days

phase 2

exenatide Subcutaneous abdominal injections of 10 microg twice daily (n=121)

vs.

placebo (n=112)

double-blind

Parallel groups

Sample size: 121/112

Primary endpoint: change from baseline in hemoglobin A1c

FU duration: 16 weeks

exenatide 5 mg then 10 mg twice-daily for 4 and 12 weeks (n=234)

vs.

placebo (n=232)

double-blind

Parallel groups

Sample size: 234/232

Primary endpoint: change in HbA1c

FU duration: 16 weeks

phase 3

Exenatide 10–20 µg daily (n=-9)

vs.

Placebo on-top of Metformin (n=113)

3 arms : exenatide 5µg twice daily, 10µg twice daily and placebo

double blind

Parallel groups

Sample size: -9/113

Primary endpoint: HbA1c

FU duration: 30 weeks

Exenatide 10µg twice daily (n=129)

vs.

Placebo on-top of SU (n=123)

3rd arms with exenatide 5µg BID

double blind (not adequate)

Sample size: 129/123

Primary endpoint: HbA1c

FU duration: 30 weeks

Exenatide 5 µg bid (n=245)

vs.

Placebo on-top of sulphonylureas+metformin (n=247)

3 arms: exenatide 5, 10µg bid or placebo

double blind

Parallel groups

Sample size: 245/247

Primary endpoint: change in HbA1c

FU duration: 30 weeks

exenatide (5 microg for 4 weeks followed by 10 microg) for 12 weeks (n=28)

vs.

placebo (n=26)

double-blind

Parallel groups

Sample size: 28/26

Primary endpoint: mean 24-hour HR

FU duration: 12 weeks

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events NaN [NaN; NaN]

EXE 10 microg b.i.d. (n=45)

vs.

ROSI 4 mg b.i.d. (n=45)

3 arms: EXE 10 microg bid (n=45), ROSI 4 mg bid (n=45), or EXE 10 microg bid + ROSI 4 mg bid (n=47)

open

Parallel groups

Sample size: 45/45

Primary endpoint:

FU duration: 20 weeks

ant hypoglycemia 0.58 [0.35; 0.97]

nausea 13.54 [5.06; 36.22]

vomiting 3.03 [1.02; 9.07]

death NaN [NaN; NaN]

CV events NaN [NaN; NaN]

diarrhoea 1.25 [0.28; 5.45]

severe hypoglycemia 0.00 [0.00; NaN]

nausea 9.57 [2.96; 30.92]

diarrhoea 2.39 [1.08; 5.32]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

CV events ∞ [NaN; ∞]

vomiting 3.19 [0.89; 11.44]

treatment-emergent adverse events (TEAEs) 1.14 [1.00; 1.30]

serious adverse events 1.05 [0.46; 2.43]

CV events 0.98 [0.14; 6.86]

Exenatide 20 µg daily (n=136)

vs.

Insulin (n=127)

open

Cross over

Sample size: 136/127

Primary endpoint: HbA1c change

FU duration: 16 weeks

exenatide (2 mg, once-a-week injection) (n=233)

vs.

insulin glargine once-daily injection (n=223)

open (blind analysis)

Parallel groups

Sample size: 233/223

Primary endpoint: HbA1c

FU duration: 26 weeks

exenatide (n=-9)

vs.

Insulin Glargine (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

exenatide(5 microg BID for 4 weeks and 10 microg BID thereafter) (n=-9)

vs.

biphasic insulin aspart 70/30 (BIAsp 30) 30 QD (12 U before supper) (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: not unique

FU duration: 24 weeks

exenatide (5 microg BID for 4 weeks and 10 microg BID thereafter) (n=-9)

vs.

biphasic insulin aspart 70/30 (BIAsp 30) 30 BID (12 U divided equally between pre-breakfast and pre-supper) (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: not unique

FU duration:

exenatide 10µg bid (n=36)

vs.

insulin glargine (n=33)

Parallel groups

Sample size: 36/33

Primary endpoint: beta-Cell function

FU duration: 52 weeks

exenatide 5¨C10 ¦Ìg bid (n=-9)

vs.

insulin glargine o.d. (titrated to target fasting plasma glucose ¡Ü5.6 mmol/l) (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=118)

vs.

(n=116)

Sample size: 118/116

Primary endpoint:

FU duration:

CV events 0.00 [0.00; NaN]

CV events 0.00 [0.00; NaN]

death NaN [NaN; NaN]

CV deaths NaN [NaN; NaN]

2 mg injected exenatide once weekly plus oral placebo once daily (n=170)

vs.

100 mg oral sitagliptin once daily plus injected placebo once weekly (n=-9)

3rd arms receiving 45 mg oral pioglitazone once daily plus injected placebo once weekly

double blind

Sample size: 170/-9

Primary endpoint: change in HbA1c

FU duration: 26 weeks

2 mg injected exenatide once weekly plus oral placebo once daily (n=170)

vs.

45 mg oral pioglitazone once daily plus injected placebo once weekly (n=172)

3rd arms receiving 100 mg oral sitagliptin once daily plus injected placebo once weekly

double blind

Parallel groups

Sample size: 170/172

Primary endpoint: change in HbA1c

FU duration: 26 weeks

exenatide subcutaneous injection (n=-9)

vs.

sitagliptin (100 mg QAM) for 2 weeks (n=-9)

double-blind

Cross over

Sample size: -9/-9

Primary endpoint: not unique

FU duration: 2 weeks

phase 4

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

exenatide 10 microg twice a day (n=63)

vs.

glibenclamide 5 mg three times a day (n=65)

Sample size: 63/65

Primary endpoint:

FU duration: