Table 2.
Overview of Exenatide Phase 3 Clinical Studies.a
| Study Citation | Ther Studied | BG Ther | DO (%) | ITT N | F (%) | White (%) | T2DM Dur (y) ±SD | BL HbA1c (%) ±SD | ΔHbA1c (%) ±SE | Achieved HbA1c ≤7% or <7% (%) | BL BMI (kg/m2) ±SD | BL Wt (kg) ±SD | ΔWt (kg) ±SE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Exenatide BID | |||||||||||||
| Bergenstal 2009 [86] | ExBID | MET + SFU | 29.8 | 124 | 51.6 | 63.7 | 9±6 | 10.2±1.5 | -1.75 | 20 | 34±7 | 96.6±24 | -1.9 |
| Aspart QD | 16.1 | 124 | 51.6 | 67.7 | 8±6 | 10.1±1.8 | -2.34 | 26 | 34±7 | 96.9±25 | 2.8 | ||
| Aspart BID | 19.4 | 124 | 52.4 | 59.7 | 10±6 | 10.3±1.9 | -2.76 | 37 | 34±7 | 93.8±24 | 4.1 | ||
| Blonde 2006 [87] | ExBID | MET +/or SFU | 43.0 | 551 | 39 | 74 | 7±6 | 8.4±1.0 | -1.1±0.1 | 48 | 34±6 | 98±20 | -4.4±0.3 |
| Bunck 2009 [88] | ExBID | MET | 16.7 | 36 | 36.1 | 100 | 6±1 | 7.6±0.1 | -0.8±0.1 | NG | 31±1 | 90.6±2.1 | -3.6 ±0.6* |
| Glarg | 9.1 | 33 | 33.3 | 97 | 4±1 | 7.4±0.1 | -0.7±0.2 | NG | 30±1 | 92.4±2.4 | 1.0±0.8 | ||
| Bunck 2011 [89] | ExBID | MET | 44.4 | 36 | 36.1 | 100 | 6±1 | 7.6±0.1 | -1.0 | NG | 31±1 | 90.6±2.1 | -5.7 ±1.3* |
| Glarg | 48.5 | 33 | 33.3 | 97 | 4±1 | 7.4±0.1 | -0.5 | NG | 30±1 | 92.4±2.4 | 2.1±1.3 | ||
| Buse 2011 [90] | ExBID | Glarg ±MET and/or TZD | 19 | 137 | 49 | 75 | 12±7 | 8.32± 0.85 | -1.74 ±0.1* | 60* | 34±6 | 95.4±20.4 | -1.8 ±0.3* |
| PBO | 18 | 122 | 36 | 80 | 12±7 | 8.50± 0.96 | -1.04 ±0.1 | 35 | 33±6 | 93.4±21.2 | 1.0±0.3 | ||
| Buse 2009 [91] | ExBID | MET ± SFU | 19.5 | 231 | 45 | 91 | 8±6 | 8.1±1.0 | -0.8±0.1 | 43 | 33±6 | 93.0±19.5 | -2.9±0.3 |
| LIRA | 14.2 | 233 | 51 | 93 | 9±6 | 8.2±1.0 | -1.1±0.1 | 54 | 33±6 | 93.1±20.1 | -3.2±0.3 | ||
| Buse 2004 [92] | ExBID | SFU | 29.5 | 129 | 42.6 | 59.7 | 7±7 | 8.6±1.2 | -0.9 ±0.1* | 34.2* | 33±6 | 95±18 | -1.6 ±0.3* |
| 5 mcg ExBID | 24.0 | 125 | 40.8 | 61.6 | 6±5 | 8.5±1.1 | -0.5 ±0.1* | 26.7* | 303±6 | 95±22 | -0.9±0.3 | ||
| PBO | 39.8 | 123 | 37.4 | 66.7 | 6±5 | 8.7±1.2 | 0.1±0.1 | 7.7 | 34±5 | 99±18 | -0.6±0.3 | ||
| Buse 2007 [93] | ExBID | MET +/or SFU | 45.7 | 521 | 41 | 74 | 8±6 | 8.4±1.1 | -1.1±0.1 | 50 | 34±6 | 99±20 | -4.7±0.3 |
| Davies 2009 [94] | ExBID | MET +/or SFU +/or TZD | 16.1 | 118 | 29.7 | NG | 9±5 | 8.7±0.7 | -1.25± 0.09 | NG | 35±6 | 101.4±19.8 | -2.7 ±0.3* |
| Glarg | 10.3 | 117 | 33.6 | NG | 8±4 | 8.5±0.7 | -1.26 ±0.09 | NG | 34±5 | 97.6±16.4 | 3.0±0.3 | ||
| DeFronzo 2005 [95] | ExBID | MET | 17.7 | 113 | 39.8 | 79.6 | 5±5 | 8.2±1.0 | -0.8 ±0.1* | 46* | 34±6 | 101±20 | -2.8 ±0.5* |
| 5 mcg ExBID | 18.2 | 110 | 48.2 | 77.3 | 6±6 | 8.3±1.1 | -0.4 ±0.1* | 32* | 34±6 | 100±22 | -1.6 ±0.4* | ||
| PBO | 21.2 | 113 | 40.7 | 72.6 | 7±6 | 8.2±1.0 | 0.1±0.1 | 13 | 34±6 | 100±19 | -0.3±0.3 | ||
| Derosa 2010 [96] | ExBID | MET | 6.3 | 63 | 52.4 | 100 | NG | 8.8±0.7 | -1.5 | NG | 29±2 | 82.0±8.3 | -8.0 |
| Gli | 12.3 | 65 | 49.2 | 100 | NG | 8.9±0.8 | -1.8 | NG | 29±1 | 82.4±9.1 | +4.3 | ||
| Derosa 2011 [97] | ExBID | MET | 8.8 | 57 | 50.9 | 100 | NG | 8.7±0.7 | -1.2 | NG | 28±1 | 80.2±7.5 | -5.1 |
| Gli | 9.3 | 54 | 51.9 | 100 | NG | 8.8±0.8 | -1.4 | NG | 29±1 | 81.4±8.1 | -0.9 | ||
| Forti 2008 [98] | ExBID at B, D | MET ± SFU ± TZD | 11.1 | 190 | 58.4 | 41.0 | 9±6 | 8.4±0.9 | -1.2±0.1 | 45.1 | 31±4 | 82.7±16.1 | -1.3±0.2 |
| ExBID at L, D | 16.0 | 187 | 51.3 | 45.0 | 8±6 | 8.5±1.0 | -1.1±0.1 | 32.6 | 31±4 | 81.8±14.2 | -1.1±0.2 | ||
| Gallwitz 2011 [99] | ExBID | MET | 25.4 | 181 | NG | NG | 5±4 | 7.9±0.8 | -1.00 | 49.2 | 33±4 | NG | -4.1 ±0.2* |
| Aspart | 20.8 | 173 | NG | NG | 5±5 | 7.9±0.9 | -1.14 | 56.6 | 33±4 | NG | 1.0± 0.2 | ||
| Gao 2009 [100] | ExBID | MET ± SFU | 17.5 | 234 | 52 | 0 | 8±6 | 8.3±1.0 | -1.2* | 48* | 26±3 | 69.6±11.2 | -1.2* |
| PBO | 10.3 | 232 | 59 | 0 | 8±5 | 8.3±1.0 | -0.4 | 17 | 26±3 | 67.9±11.0 | -0.1 | ||
| Gill 2010 [101] | ExBID | MET +/or TZD | 21.4 | 28 | 32 | 86 | 7±4 | 7.5±0.9 | NG | NA | 30±3 | 91.6±15.2 | -1.8 ±0.4* |
| PBO | 11.5 | 26 | 58 | 96 | 6±4 | 7.1±0.7 | NG | NA | 30±4 | 85.9±12.2 | -0.3±0.4 | ||
| Heine 2005 [102] | ExBID | MET + SFU | 19.1 | 282 | 45.0 | 79.8 | 10±6 | 8.2±1.0 | -1.1 | 46 | 31±4 | 87.5±16.9 | -2.3* |
| Glarg | 9.4 | 267 | 43.4 | 80.5 | 9±6 | 8.3±1.0 | -1.1 | 48 | 31±5 | 88.3±17.9 | +1.8 | ||
| Kadowaki 2009 [103] | ExBID | SFU ±MET or ±TZD | 16.2 | 38 | 37.8 | 0 | 10± 6 | 7.9±0.9 | -1.4 ±0.1* | 79.4* | 26±5 | 70.3±15.9 | -1.3±0.3 |
| 5.0 mcg ExBID | 10.8 | 37 | 32.4 | 0 | 11± 6 | 7.9±0.8 | -1.2 ±0.1* | 71.4* | 25±3 | 65.6±9.8 | -0.2±0.3 | ||
| 2.5 mcg ExBID | 8.1 | 38 | 29.7 | 0 | 15±11 | 8.0±0.8 | -0.9 ±0.1* | 50.0* | 24±3 | 64.9±11.6 | -0.08±0.2 | ||
| PBO | 2.5 | 40 | 25.0 | 0 | 12±6 | 8.1±0.7 | 0.02± 0.1 | 5.1 | 26±5 | 71.1±14.0 | -0.7±0.2 | ||
| Kadowaki 2011 [104] | ExBID | SFU±MET or SFU±TZD | 27.4 | 72 | 31.9 | 0 | 12±7 | 8.2±1.0 | -1.6* ±0.1 | 71.0* | 26±4 | 69.1±11.2 | -1.5 ±0.3* |
| 5 mcg ExBID | 9.7 | 72 | 31.9 | 0 | 12±6 | 8.3±0.8 | -1.3 ±0.1* | 67.1* | 25±4 | 67.0±11.5 | -0.4±0.3 | ||
| PBO | 5.7 | 35 | 31.4 | 0 | 12±7 | 8.1±0.9 | -0.3±0.2 | 15.2 | 26±4 | 70.3±13.3 | -0.5±0.4 | ||
| Kendall 2005 [105] | ExBID | MET + SFU | 17.8 | 241 | 40.7 | 66.4 | 9±6 | 8.5±1.1 | -0.8 ±0.1* | 30* | 34±6 | 98±21 | -1.6 ±0.2* |
| 5 mcg ExBID | 15.9 | 245 | 40.8 | 69.0 | 9±6 | 8.5±1.0 | -0.6 ±0.1* | 24* | 33±6 | 97±19 | -1.6 ±0.2* | ||
| PBO | 23.9 | 247 | 44.1 | 68.4 | 9±6 | 8.5±1.0 | 0.2±0.1 | 7 | 34±5 | 99±19 | -0.9±0.2 | ||
| Klonoff 2008 [106] | ExBID | MET, + SFU | 58.8 | 527 | 36 | 83 | 8±6 | 8.2±1.0 | -1.0±0.1 | 46 | 34±5 | 99±18 | -5.3±0.4 |
| Liukus 2010 [107] | ExBID | TZD ± MET | 14 | 111 | 40 | 57 | 6±4 | 8.2±0.9 | -0.8 ±0.2* | 49 | 34±6 | 94.5±17.8 | -1.4±0.6 |
| PBO | 7 | 54 | 43 | 61 | 6±5 | 8.3±0.9 | -0.1±0.2 | 36 | 33±5 | 92.6±18.0 | -0.8±0.7 | ||
| Moretto 2008 [108] | ExBID | D/E | 14 | 78 | 38 | 72 | 2±3 | 7.8±1.0 | -0.9 ±0.1* | 46* | 31±5 | 86±16 | -3.1 ±0.3* |
| 5 mcg ExBID | 13 | 77 | 48 | 65 | 2±3 | 7.9±1.0 | -0.7 ±0.1* | 48* | 32±5 | 85±15 | -2.8 ±0.3* | ||
| PBO | 12 | 77 | 45 | 66 | 1±2 | 7.8±1.0 | -0.2±0.1 | 29 | 32±5 | 86±16 | -1.4±0.3 | ||
| Nauck 2007 [109] | ExBID | MET + SFU | 21.3 | 253 | 47 | NG | 10±6 | 8.6±1.0 | -1.0±0.1 | 32* | 31±4 | 85.5±15.7 | -2.5 ±0.2* |
| Aspart | 10.1 | 248 | 51 | NG | 10± 6 | 8.6±1.1 | -0.9±0.1 | 24 | 30±4 | 83.4±15.6 | 2.9±0.2 | ||
| Ratner 2006 [110] | ExBID | MET | 39 | 150 | 31 | 86 | 5±5 | 8.1±1.0 | -1.3±0.1 | 59 | 34±6 | 102±21 | -5.3±0.8 |
| Riddle 2006 [111] | ExBID | SFU ± MET | 45 | 401 | 39 | 75 | 8±6 | 8.4±1.0 | -1.0±0.1 | 44 | 34±6 | 99±21 | -4.0±0.3 |
| Zinman 2007 [112] | ExBID | TZD ± MET | 28.9 | 121 | 46.3 | 85.1 | 7±5 | 7.9±0.9 | -0.9 ±0.1* | 62* | 34±5 | 97.5±18.8 | -1.8 ±0.3* |
| PBO | 14.3 | 112 | 42.9 | 82.1 | 8±6 | 7.9±0.8 | 0.1±0.1 | 16 | 34±5 | 96.9±19.0 | -0.2±0.3 | ||
| Exenatide QW | |||||||||||||
| Bergenstal 2010 [113] DURATION-2 | ExQW | MET | 20.6 | 160 | 44 | 33 | 6±5 | 8.6±1.2 | -1.5* | ~58* | 32±5 | 89±20 | -2.3* |
| 100 mg SITA | 13.3 | 166 | 48 | 30 | 5±4 | 8.5±1.2 | -0.9 | ~30 | 32±5 | 87±20 | -0.8 | ||
| 45 mg PIO | 20.6 | 165 | 52 | 39 | 6±5 | 8.5±1.1 | -1.2 | ~42 | 32±6 | 88±20 | 2.8 | ||
| Blevins 2011 [114] DURATION-5 | ExQW | D/E, MET, SFU, TZD or any comb | 15.5 | 129 | 40 | 63 | 7±5 | 8.5±1.1 | -1.6 ±0.1* | 58.1* | 34±6 | 97.0±20.7 | -2.3±0.4 |
| ExBID | 22.8 | 123 | 45 | 55 | 7±5 | 8.4±1.2 | -0.9±0.1 | 30.1 | 33±5 | 94.3±18.9 | -1.4±0.4 | ||
| Buse 2010 [115] DURATION-1 | ExQW | D/E, MET, SFU, TZD or 2 OAD | 19 | 148 | 43 | 83 | 7±6 | 8.3±1.0 | -2.0 | 71 | 35±5 | 103±19 | -4.1 |
| ExBID then ExQW | 18 | 147 | 47 | 74 | 6±5 | 8.2±0.9 | -2.0 | 71 | 35±5 | 102±20 | -4.5 | ||
| Buse 20111 | ExQW | MET, SFU, TZD, or any comb | 13.2 | 461 | 44.9 | 83.3 | 8±6 | 8.4±1.0 | -1.3 | 52.3 | 32±6 | 90.9±19.5 | -2.7 |
| LIRA | 13.1 | 450 | 45.6 | 81.8 | 9±7 | 8.4±1.0 | -1.5 | 60.2 | 32±5 | 91.1±19.1 | -3.6 | ||
| Diamant 2010 [116] | ExQW | MET ± SFU | 10.3 | 233 | 48 | 82 | 8±6 | 8.3±1.1 | -1.5 ±0.1* | 60* | 32±5 | 91.2±18.6 | -2.6 ±0.2* |
| Glarg | 6.3 | 223 | 45 | 85 | 8±6 | 8.3±1.0 | -1.3±0.1 | 48 | 32±5 | 90.6±16.4 | 1.4±0.2 | ||
| Drucker 2008 [117] | ExQW | D/E, MET, SFU, TZD or 2 OAD | 13.5 | 148 | 45.0 | 83 | 7±6 | 8.3±1.0 | -1.9 ±0.1* | 77* | 35±5 | 102±19 | -3.7±0.5 |
| ExBID | 11.6 | 147 | 49.0 | 73 | 6±5 | 8.3±1.0 | -1.5±0.1 | 61 | 35±5 | 102±21 | -3.6±0.5 | ||
| MacConell 20112 | ExQW | D/E, MET, SFU, TZD or 2 OAD | 34 | 295 | NG | NG | 7±5 | 8.2±1.0 | -1.6 | 57 | NG | 101±18 | -2.3 |
| Russell-Jones 2012 [118] | ExQW | D/E | 15.3 | 248 | 44 | 68.1 | 3±3 | 8.5±1.2 | -1.5±0.1 | 63 | 31±5 | 88±19 | -2.0±0.2 |
| MET | 13.4 | 246 | 37 | 65.0 | 3±4 | 8.6±1.2 | -1.5±0.1 | 55 | 31±6 | 86±20 | -2.0±0.2 | ||
| PIO | 18.4 | 163 | 41 | 67.5 | 3±4 | 8.5±1.2 | -1.6±0.1 | 61 | 31±5 | 86±18 | 1.5±0.3 | ||
| SITA | 14.1 | 163 | 42 | 69.3 | 3±4 | 8.5±1.3 | -1.2±0.1 | 43 | 32±5 | 89±19 | -0.8±0.3 | ||
| Taylor 2011 [119] | ExQW | D/E, MET, SFU, TZD or 2 OAD | 27 | 295 | 47 | 79 | 7±5 | 8.2±1.0 | -1.7±0.1 | 60 | 35±5 | 101±19 | -2.6±0.5 |
| Wysham 2011 [120] | ExQW | MET | 35.6 | 160 | 43 | 32 | 6±5 | 8.6±1.2 | -1.6±0.1 | 58 | 32±5 | 90±19 | -1.8±0.5 |
| SITA then ExQW | 21.7 | 166 | 42 | 35 | 6±5 | 8.5±1.1 | -1.8±0.5 | 53 | 32±5 | 88±21 | -1.1±0.3 | ||
| PIO then EQW | 39.4 | 165 | 49 | 39 | 6±5 | 8.4±1.0 | -1.6±0.1 | 59 | 32±5 | 86±21 | -3.0±0.3 | ||
Note: when 'ExBID' is listed without dose, dose was 10 mcg BID. When ExQW listed without dose, dose was 2 mg.
*
p<0.05 improvement in HbA1c or weight versus control group.
a
Portions of table adapted from: Aroda V, Henry R, Han J, et al. A meta-analysis and systematic review of the efficacy of GLP-1 receptor agonists and DPP-4 inhibitors. Clin Ther. 2012;34:1247-58.e22