Table 3.
Overview of Nausea, Vomiting, Hypoglycemia, and Selected Treatment-Emergent Adverse Events from Phase 3 Exenatide Clinical Trials
| Citation | Treatment | Nausea (%) | Vomiting (%) | Hypo (%) | Major/ Severe Hypo? | Other Relevant Observations |
|---|---|---|---|---|---|---|
| EXENATIDE BID CLINICAL TRIALS | ||||||
| Bergenstal 2009 [86] | ExBID+MET+SFU | 29 | NG | 29 | No | 1.28 hypo/subj-y. |
| Aspart QD+MET+SFU | 9 | NG | 56 | 3.2% | 4.02 hypo/subj-y. P=0.0013 vs Ex | |
| Aspart BID+MET+SFU | 8 | NG | 61 | 4.8% | 5.25 hypo/subj-y. P<0.0001 vs Ex | |
| Blonde 2006 [87] | ExBID+MET +/or SFU | 14-29 | NG | 7-12 | 0.7% | The severe hypo event occurred in a patient treated with SFU |
| Bunck 2009 [88] | ExBID+MET | 50 | NG | 8.3 | No | 1 pancreatitis, resolved after Ex stopped |
| Glarg+MET | NG | NG | 24.2 | No | ||
| Bunck 2011 [89] | ExBID+MET | 38.1 | 9.5 | 19.0 | No | |
| Glarg+MET | NG | 8.0 | 28.0 | No | ||
| Buse 2011 [90] | ExBID+Glarg | 41 | 18 | 25.0 | No | 1.4 hypo/subj-y Nocturnal: 17% hypo |
| PBO+Glarg | 8 | 4 | 29.0 | 1% | 1.2 hypo/subj-y. P=0.49 vs Ex Nocturnal: 26% hypo |
|
| Buse 2009 [91] | ExBID+MET±SFU | 28.0 | 9.9 | 34.5 | 0.9% | 2.6 minor hypo/subj-y. Major hypo had SFU |
| LIRA+MET±SFU | 25.5 | 6.0 | 26.0 | No | 1.9 minor hypo/subj-y. P=0.0131 vs Ex 1 mild pancreatitis | |
| Buse 2004 [92] | ExBID+MET +/or SFU | 51 | 13 | 36 | No | |
| 5 mcg ExBID+MET +/or SFU | 39 | 10 | 14 | No | ||
| PBO+MET +/or SFU | 7 | 2 | 3 | No | ||
| Buse 2007 [93] | ExBID+MET +/or SFU | 8-39 | NG | <1-13 | 0.2% | 1 severe hypo in 1010 subj-y |
| Davies 2009 [94] | ExBID+MET+/or SFU+/or TZD | 48.3 | NG | 50.0 | 4.2% | Nocturnal hypo: 11.9%. |
| Glarg+MET+/or SFU+/or TZD | 2.6 | NG | 59.6 | 5.3% | Nocturnal hypo: 29.8%. P=0.001 vs Ex | |
| DeFronzo 2005 [95] | ExBID+MET | 45 | 12 | 5 | No | |
| 5 mcg ExBID+MET | 36 | 11 | 5 | No | ||
| PBO+MET | 23 | 4 | 5 | No | ||
| Derosa 2010 [96] | ExBID+MET | NG | NG | 0 | NG | |
| Glibenclamide+MET | NG | NG | 4.6 | NG | ||
| Derosa 2011 [97] | ExBID+MET | NG | NG | 0 | NG | |
| Glibenclamide+MET | NG | NG | 5.6 | NG | ||
| Forti 2008 [98] | ExBID at B/D+MET± SFU±TZD | 22.6 | 10.0 | NG | 4.2% | 5.21 hypo/subj-y. P=0.393 vs Ex L/D |
| ExBID at L/D+MET± SFU± TZD | 25.1 | 10.2 | NG | 0.5% | 6.51 hypo/subj-y | |
| Gallwitz 2011 [99] | ExBID+MET | 18.8 | 9.9 | 8.0 | No | Nocturnal hypo: 3.9% |
| Aspart+MET | NG | NG | 20.5 | No | Nocturnal hypo: 7.0% | |
| Gao 2009 [100] | ExBID+MET±SFU | 25.5 | 15.8 | 35.5 | 0.9% | 4.4 hypo/subj-y. MET only: 1.8 hypo/subj-y MET+SFU: 4.7 hypo/subj-y |
| PBO+MET±SFU | 0.9 | 0 | 9.0 | 0.4% | 0.5 hypo/subj-y MET only: 0.22 hypo/subj-y MET+SFU: 0.54 hypo/subj-y |
|
| Gill 2010 [101] | ExBID+MET +/or TZD | 36 | NG | 7 | No | |
| PBO+MET +/or TZD | 19 | NG | 4 | No | ||
| Heine 2005 [102] | ExBID+MET+SFU | 57.1 | 17.4 | NG | 1.4% | 7.3 hypo/subj-y. Nocturnal hypo: 21%; 0.9 hypo/subj-y |
| Glarg+MET+SFU | 8.6 | 3.7 | NG | 1.5% | 6.3 hypo/subj-y. Nocturnal hypo: 43%; 2.4 hypo/subj-y |
|
| Kadowaki 2009 [103] | ExBID+SFU±MET, +SFU±TZD | 35.1 | 8.1 | 54.1 | No | |
| 5 mcg ExBID+SFU±MET, +SFU±TZD | 8.1 | 13.5 | 43.2 | No | ||
| 2.5 mcg ExBID+SFU± MET, +SFU±TZD | 10.8 | 5.4 | 27.0 | No | ||
| PBO+SFU±MET, +SFU±TZD | 0 | 0 | 10.0 | No | ||
| Kadowaki 2011 [104] | ExBID+SFU, +SFU+MET, +SFU+TZD | 36.1 | 16.7 | 58.3 | No | |
| 5 mcg ExBID+SFU, +SFU+MET, +SFU+TZD | 25.0 | 4.2 | 51.4 | No | ||
| PBO+ExBID+SFU, +SFU+MET, +SFU+TZD | 8.6 | 2.9 | 22.9 | No | ||
| Kendall 2005 [105] | ExBID+MET+SFU | 48.5 | 13.7 | 27.8 | No | Lower hypo incidence in SFU MIN group |
| 5 mcg ExBID+MET+SFU | 39.2 | 14.7 | 19.2 | 4.1% | ||
| PBO+MET+SFU | 20.6 | 4.5 | 12.6 | No | ||
| Klonoff 2008 [106] | ExBID+MET+SFU | 59.0 | NG | 40.0 | 0.2% | All severe hypo events occurred in patients treated with SFU |
| Liukus 2010 [107] | ExBID+TZD±MET | 12 | 8 | 4.0 | No | |
| PBO+TZD±MET | 2 | 0 | 2.0 | No | ||
| Moretto 2008 [108] | ExBID | 13 | 4 | 4 | No | 0.52 hypo/subj-y |
| 5 mcg ExBID | 3 | 4 | 5 | No | 0.21 hypo/subj-y | |
| PBO | 0 | 0 | 1 | No | 0.03 hypo/subj-y. P=0.014 vs Ex | |
| Nauck 2007 [109] | ExBID+MET+SFU | 33.2 | 15.0 | NG | No | 4.7±0.7 hypo/subj-y Nocturnal hypo: 17%. |
| Aspart+MET+SFU | 0.4 | 3.2 | NG | No | 5.6±0.7 hypo/subj-y Nocturnal hypo: 25%; P<0.038 vs Ex |
|
| Ratner 2006 [110] | ExBID+MET | 14-33 | 1-5 | NG | No | |
| Riddle 2006 [111] | ExBID+SFU±MET | 14-27 | NG | 8-15 | 1.0% | |
| Zinman 2007 [112] | ExBID+TZD±MET | 39.7 | 13.2 | 10.7 | No | |
| PBO+TZD±MET | 15.2 | 0.9 | 7.1 | No | ||
| EXENATIDE QW CLINICAL TRIALS | ||||||
| Bergenstal 2010 [113] | ExQW+MET | 24 | 11 | 1 | No | |
| SITA+MET | 10 | 2 | 3 | No | ||
| PIO+MET | 5 | 3 | 1 | No | 2 cases of pancreatitis | |
| Blevins 2011 [114] | ExQW+D/E, MET, SFU, TZD or any combo | 14.0 | 4.7 | 3.9 | No | All hypo events occurred in patients treated with SFU 1 case pancreatitis: resolved while taking ExQW. |
| ExBID+D/E, MET, SFU, TZD or any combo | 35.0 | 8.9 | 3.3 | No | All hypo events occurred in patients treated with SFU | |
| Buse 2010 [115] | ExQW+D/E, MET, SFU, TZD or 2 OADs | 7.0 | 6.3 | NG | No | All hypo events occurred in patients treated with SFU Wk 30-52: 10.2% hypo |
| ExBID then ExQW, +D/E, MET, SFU, TZD or 2 OADs | 7.7 | 4.6 | NG | No | All hypo events occurred in patients treated with SFU Wk 30-52: 8.0% hypo |
|
| Buse 20111 | ExQW+MET, SFU, TZD or any comb | 9.3 | 3.7 | 10.8 | No | |
| LIRA+MET, SFU, TZD or any comb | 20.4 | 10.7 | 8.9 | No | ||
| Diamant 2010 [116] | ExQW+MET±SFU | 13 | 4 | 8 | No | |
| Glarg+MET±SFU | 1 | 1 | 26 | No | Hypo with MET: p<0.0001 vs Ex+MET Hypo with MET+SFU: p=0.0009 vs Ex+MET+SFU Nocturnal hypo Hypo with MET: p=0.028 vs Ex+MET Hypo with MET+SFU: p=0.0005 vs Ex+MET+SFU |
|
| Drucker 2008 [117] | ExQW+D/E, MET, SFU, TZD or 2 OADs | 26.4 | 10.8 | 5.4 | No | Hypo with SFU: 14.5% vs 0% without SFU |
| ExBID then ExQW, +D/E, MET, SFU, TZD or 2 OADs | 34.5 | 18.6 | 6.1 | No | Hypo with SFU: 15.4% hypo vs 1.1% without SFU | |
| MacConell 20112 | ExQW+D/E, MET, SFU, TZD or 2 OADs | 16 (wks 30- 156) | NG | NG | No | |
| Russell-Jones 2012 [118] | ExQW | 11.3 | 4.8 | 5.2 | No | |
| MET | 6.9 | 3.3 | 4.1 | No | ||
| PIO | 4.3 | 3.1 | 3.7 | No | ||
| SITA | 3.7 | 1.8 | 3.1 | No | ||
| Taylor 2011 [119] | ExQW+D/E, MET, SFU, TZD or 2 OADs | 12* | 9* | 6.6* | No | *Wk 30-104 Hypo with SFU: 94% (16/17 subj) |
| Wysham 2011 [120] | ExQW+MET | 5.0** | 5.0** | 1** | No | **Wk 26-52 |
| SITA then ExQW, +MET | 10.8** | 3.8** | 2** | No | **Wk 26-52 | |
| PIO then ExQW, +MET | 9.6** | 2.6** | 1** | No | **Wk 26-52 | |
Note: when 'ExBID' is listed without dose, dose was 10 mcg BID. When ExQW listed without dose, dose was 2 mg.
Abbreviations: Aspart insulin aspart; B, breakfast; BID, twice daily; D, dinner; Ex, exenatide; GLARG, insulin glargine; Hypo, hypoglycemic events; hypo/subj-y, number of hypoglycemic events per subject year; L, lunch; MET, metformin; MIN, minimum; Lira, liraglutide; NG, not given; PBO, placebo; PIO, pioglitazone; QW, once weekly; Sita, sitagliptin; Subj, subject; SFU, sulfonylurea; TZD, thiazolidinedione; vs, versus; Wk, week; Y, year.