In the original article, there was a mistake in Table 2. Adverse effects and safety risks in phase 3 trials as published. Three values in the row for SUSTAIN 6, s.c semaglutide 1 mg were accidentally transposed to the incorrect column. The corrected Table 2 appears below.
Table 2
| Treatment arms | Incidence of AE, n (%) | % of patients with AE leading to trial product discontinuation | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any | Severe or confirmed symptomatic hypoglycemic episode* | Gastrointestinal | Pancreas | Gallbladder | Thyroid | Diabetic retinopathy | Acute kidney Injury | Any AE, n(%) | Gastrointestinal, % | ||||
| Nausea | Vomiting | Diarrhea | Pancreatitis | Pancreatic cancer | |||||||||
| PIONEER 1 | |||||||||||||
| Oral semaglutide 3 mg | 101 (57.7) | 5 (2.9) | 14 (8.0) | 5 (2.9) | 15 (8.6) | 0 | NR | 0 | 1 (0.6%) | 0 | 4 (2.3) | 75 | |
| Oral semaglutide 7 mg | 93 (53.1) | 2 (1.1) | 9 (5.1) | 8 (4.6) | 9 (5.1) | 0 | NR | 0 | 6 (3.4%) | 0 | 7 (4.0) | 57 | |
| Oral semaglutide 14 mg | 99 (56.6) | 1 (0.6) | 28 (16.0) | 12 (6.9) | 9 (5.1) | 0 | NR | 0 | 2 (1.1%) | 1 (0.6) | 13 (7.4) | 69 | |
| Placebo | 99 (55.6) | 1 (0.6) | 10 (5.6) | 4 (2.2) | 4 (2.2) | 0 | NR | 0 | 3 (1.7%) | 1 (0.6) | 4 (2.2) | 25 | |
| PIONEER 2 | |||||||||||||
| Oral semaglutide 14 mg | 289 (70.5) | 7 (1.7) | 81 (19.8) | 30 (7.3) | 38 (9.3) | 1 (0.2) | 0 | NR | 0 | 14 (3.4) | 2 (0.5) | 44 (10.7) | 75 |
| Empagliflozin 25 mg | 283 (69.2) | 8 (2.0) | 10 (2.4) | 7 (1.7) | 13 (3.2) | 1 (0.2) | 0 | NR | 0 | 5 (1.2%) | 1 (0.2) | 18 (4.4) | 17 |
| PIONEER 3 | |||||||||||||
| Oral semaglutide 3 mg | 370 (79.4) | 23 (4.9) | 34 (7.3) | 13 (2.8) | 45 (9.7) | 1 (0.2) | 0 | NR | 0 | 27 (5.8) | 3 (0.6) | 26 (5.6) | 42 |
| Oral semaglutide 7 mg | 363 (78.2) | 24 (5.2) | 62 (13.4) | 28 (6.0) | 53 (11.4) | 1 (0.2) | 0 | NR | 0 | 24 (5.2) | 2 (0.4) | 27 (5.8) | 56 |
| Oral semaglutide 14 mg | 370 (79.6) | 36 (7.7) | 70 (15.1) | 42 (9.0) | 57 (12.3) | 1 (0.2) | 1 (0.2) | NR | 0 | 16 (3.4) | 5 (1.1) | 54 (11.6) | 59 |
| Sitagliptin 100 mg | 388 (83.3) | 39 (8.4) | 32 (6.9) | 19 (4.1) | 37 (7.9) | 1 (0.2) | 1 (0.2) | NR | 0 | 27 (5.8) | 3 (0.6) | 24 (5.2) | 50 |
| PIONEER 4 | |||||||||||||
| Oral semaglutide 14 mg | 229 (80) | 2 (1) | 56 (20) | 25 (9) | 43 (15) | 0 | 0 | NR | 1 (0.4) | 8 (3) | 0 | 31 (11) | 71 |
| Liraglutide 1.8 mg (s.c.) | 211 (74) | 7 (2) | 51 (18) | 13 (5) | 31 (11) | 1 (0.4) | 1 (0.4) | NR | 1 (0.4) | 4 (1) | 1 (0.4) | 26 (9) | 65 |
| Placebo | 95 (67) | 3 (2) | 5 (4) | 3 (2) | 11 (8) | 1 (0.7) | 0 | NR | 0 | 2 (1) | 1 | 5 (4) | 60 |
| PIONEER 5 | |||||||||||||
| Oral semaglutide 14 mg | 122 (75) | 9 (6) | 31 (19) | 19 (12) | 17 (10) | 0 | 0 | NR | 0 | 5 (3) | 3 (1.8) | 24 (15) | 79 |
| Placebo | 109 (68) | 3 (2) | 12 (7) | 6 (4) | 6 (4) | 0 | 0 | NR | 0 | 2 (1) | 1 (0.6) | 8 (5) | 38 |
| PIONEER 6 | |||||||||||||
| Oral semaglutide 14 mg | NR | NR | NR | NR | NR | 1 (0.1) | 0 | NR | 2 (0.1) | 93 (5.8) | 32 (2.0) | 184 (11.6) | 59 |
| Placebo | NR | NR | NR | NR | NR | 3 (0.2) | 0 | NR | 0 | 76 (4.8) | 37 (2.3) | 104 (6.5) | 25 |
| PIONEER 7 | |||||||||||||
| Oral semaglutide (flexible 3, 7 or 14 mg) | 197 (78) | 14 (5.5) | 53 (21) | 14 (6) | 22 (9) | 0 | 0 | NR | 0 | 6 (2.4) | 1 (0.4) | 22 (9) | 64 |
| Sitagliptin 100 mg | 172 (69) | 14 (5.6) | 6 (2) | 3 (1) | 8 (3) | 0 | 0 | NR | 0 | 6 (2.4) | 0 | 8 (3) | 25 |
| PIONEER 8 | |||||||||||||
| Oral semaglutide 3 mg | 137 (74.5) | 52 (28.3) | 21 (11.4) | 11 (6.0) | 16 (8.7) | 0 | 0 | NR | 0 | 7 (3.8) | 2 (1.1) | 13 (7.1) | 69 |
| Oral semaglutide 7 mg | 142 (78.5) | 47 (26.0) | 30 (16.6) | 14 (7.7) | 22 (12.2) | 0 | 0 | NR | 0 | 8 (4.4) | 1 (0.6) | 16 (8.8) | 75 |
| Oral semaglutide 14 mg | 151 (83.4) | 48 (26.5) | 42 (23.2) | 18 (9.9) | 27 (14.9) | 0 | 0 | NR | 0 | 9 (5.0) | 0 | 24 (13.3) | 79 |
| Placebo | 139 (75.5) | 54 (29.3) | 13 (7.1) | 7 (3.8) | 11 (6.0) | 0 | 0 | NR | 0 | 8 (4.3) | 0 | 5 (2.7) | 20 |
| PIONEER 9 | |||||||||||||
| Oral semaglutide 3 mg | 37 (76) | 0 | 2 (4) | NR | 4 (8) | 0 | 0 | NR | 0 | 0 | 0 | 1 (2) | 100 |
| Oral semaglutide 7 mg | 37 (76) | 0 | 5 (10) | NR | 1 (2) | 0 | 0 | NR | 1 | 1 (2.0) | 0 | 1 (2) | 100 |
| Oral semaglutide 14 mg | 34 (71) | 0 | 4 (8) | NR | 3 (6) | 0 | 0 | NR | 0 | 1 (2.1) | 0 | 2 (4) | 100 |
| Liraglutide 0.9 mg (s.c.) | 32 (67) | 2 (4.2) | 0 | NR | 2 (4) | 0 | 0 | NR | 0 | 0 | 0 | 0 | 0 |
| Placebo | 39 (80) | 0 | 1 (2) | NR | 1 (2) | 0 | 0 | NR | 0 | 2 (4.1) | 0 | 0 | 0 |
| PIONEER 10 | |||||||||||||
| Oral semaglutide 3 mg | 101 (77) | 3 (2) | 7 (5) | 3 (2) | 2 (2) | 0 | 0 | 2 (2) | 0 | 9 (7) | 0 | 4 (3) | 50 |
| Oral semaglutide 7 mg | 106 (80) | 3 (2) | 11 (8) | 6 (5) | 2 (2) | 0 | 0 | 1 (1) | 0 | 12 (9) | 0 | 8 (6) | 50 |
| Oral semaglutide 14 mg | 111 (85) | 4 (3) | 12 (9) | 9 (7) | 10 (8) | 0 | 0 | 0 | 0 | 7 (5) | 0 | 8 (6) | 63 |
| Dulaglutide 0.75 mg (s.c.) | 53 (82) | 0 | 6 (9) | 1 (2) | 4 (6) | 0 | 0 | 1 (2) | 0 | 3 (5) | 0 | 2 (3) | 50 |
| SUSTAIN 1 | |||||||||||||
| S.c. semaglutide 0.5 mg | 82 (64) | 0 | 26 (20) | 5 (4) | 16 (13) | 0 | 0 | 3 (2) | 0 | NR | 0 | 8 (6) | 63 |
| S.c. semaglutide 1 mg | 73 (56) | 0 | 31 (24) | 9 (7) | 14 (11) | 0 | 0 | 1 (<1) | 0 | NR | 0 | 7 (5) | 57 |
| Placebo | 69 (53) | 3 (2) | 10 (8) | 2 (2) | 3 (2) | 0 | 0 | 0 | 0 | NR | 0 | 3 (2) | 33 |
| SUSTAIN 2 | |||||||||||||
| S.c. semaglutide 0.5 mg | 306 (75) | 7 (2) | 73 (18) | 33 (8) | 54 (13) | 3 (1%) | NR | 1 (<1) | 0 | 1 (<1) | NR | 33 (8) | 82 |
| S.c. semaglutide 1 mg | 292 (71) | 2 (<1) | 72 (18) | 41 (10) | 53 (13) | 1 (<1) | NR | 7 (2) | 1 | 0 | NR | 39 (10) | 79 |
| Sitagliptin 100 | 292 (72) | 5 (1) | 30 (7) | 11 (3) | 29 (7) | 0 | NR | 6 (1) | 0 | 3 (1) | NR | 12 (3) | 25 |
| SUSTAIN 3 | |||||||||||||
| S.c. semaglutide 1 mg | 303 (75) | 33 (8.2) | 90 (22.3) | 29 (7.2) | 46 (11.4) | 2 (<1) | NR | 6 (1%) | NR | NR | NR | 38 (9.4) | NR |
| Exenatide ER 2.0 mg | 309 (76.3) | 33 (8.1) | 48 (11.9) | 25 (6.2) | 34 (8.4) | 3 (<1) | NR | 2 (<1) | NR | NR | NR | 29 (7.2) | NR |
| SUSTAIN 4 | |||||||||||||
| S.c. semaglutide 0.5 mg | 253 (70) | 16 (4) | 77 (21) | 24 (7) | 59 (16) | 2 (1) | 1 (<1) | 1 (<1) | NR | 1 (<1) | NR | 20 (6) | 55 |
| S.c. semaglutide 1 mg | 264 (73) | 20 (6) | 80 (22) | 37 (10) | 69 (19) | 0 | 0 | 2 (1) | NR | 0 | NR | 27 (8) | 70 |
| Insulin glargine | 235 (65) | 38 (11) | 13 (4) | 11 (3) | 16 (4) | 0 | 0 | 0 | NR | 1 (<1) | NR | 4 (1) | 0 |
| SUSTAIN 5 | |||||||||||||
| S.c. semaglutide 0.5 mg | 91 (68.9) | 11 (8.3) | 15 (11.4) | 8 (6.1) | 6 (4.5) | 0 | 0 | 3 (2.3) | 0 | (3.0) | NR | 6 (4.5) | NR |
| S.c. semaglutide 1 mg | 84 (64.1) | 14 (10.7) | 22 (16.8) | 15 (11.5) | 9 (6.9) | 0 | 0 | 1 (0.8) | 0 | (0.8) | NR | 8 (6.1) | NR |
| Placebo | 77 (57.9) | 7 (5.3) | 6 (4.5) | 4 (3.0) | 2 (1.5) | 0 | 0 | 0 | 0 | 0 | NR | 1 (0.8) | NR |
| SUSTAIN 6 | |||||||||||||
| S.c. semaglutide 0.5 mg | 740 (89.6) | 191 (23.1) | 143 (17.3) | 14 (1.7) | 15 (1.8) | 6 (0.7) | 0 | 25 (3) | 0 | 42 (5.1) | 95 (11.5) | 49 | |
| S.c. semaglutide 1 mg | 732 (89.1) | 178 (21.7) | 180 (21.9) | 23 (2.8) | 19 (2.3) | 3 (0.4) | 1 (0.1) | 17 (2.1) | 0 | 50 (3.0) | 23 (2.8) | 119 (14.5) | 65 |
| Placebo | 1484 (90) | 350 (21.2) | 129 (7.8) | 5 (0.3) | 7 (0.4) | 12 (0.7) | 4 (0.2) | 39 (2.3) | 0 | 29 (1.8) | 34 (4.1) | 110 (6.7) | 16 |
| SUSTAIN 7 | |||||||||||||
| S.c. semaglutide 0.5 mg | 204 (68) | 2 (1) | 68 (23) | 31 (10) | 43 (14) | 0 | 0 | 2 (1) | 1 (<1) | 2 (1) | NR | 24 (8) | 67 |
| S.c. semaglutide 1 mg | 207 (69) | 5 (2) | 63 (21) | 31 (10) | 41 (14) | 0 | 0 | 4 (1) | 0 | 2 (1) | NR | 29 (10) | 62 |
| Dulaglutide 0.75 mg (s.c.) | 186 (62) | 3 (1) | 39 (13) | 12 (4) | 23 (8) | 0 | 0 | 4 (1) | 0 | 2 (1) | NR | 14 (5) | 43 |
| Dulaglutide 1.5 mg (s.c.) | 221 (74) | 5 (2) | 60 (20) | 29 (10) | 53 (18) | 0 | 0 | 8 (3) | 1 (<1) | 3 (1) | NR | 20 (7) | 70 |
| SUSTAIN 8 | |||||||||||||
| S.c. semaglutide 1 mg | 298 (76) | 53 (14) | 89 (23) | 50 (13) | 60 (15) | NR | NR | NR | NR | 9 (2) | 4 (1) | 38 (10) | 68 |
| Canagliflozin 300 mg | 283 (72) | 32 (8) | 26 (7) | 9 (2) | 37 (9) | NR | NR | NR | NR | 15 (4) | 0 | 20 (5) | 20 |
| SUSTAIN 9 | |||||||||||||
| S.c. semaglutide 1 mg | 104 (69.3) | 17 (11.3) | 29 (19.3) | 14 (9.3) | 17 (11.3) | 0 | 0 | NR | NR | 3 (2.0) | 1 (0.7) | 13 (8.7) | 77 |
| Placebo | 91 (60.3) | 3 (2.0) | 5 (3.3) | 3 (2.0) | 9 (6.0) | 0 | 0 | NR | NR | 8 (5.3) | 0 | 3 (2.0) | 0 |
| SUSTAIN 10 | |||||||||||||
| S.c. semaglutide 1 mg | 204 (70.6) | 5 (1.7) | 63 (21.8) | 30 (10.4) | 45 (15.6) | 0 | NR | NR | NR | 3 (1.0) | NR | 33 (11.4) | 67 |
| Liraglutide 1.2 mg (s.c.) | 190 (66.2) | 7 (2.4) | 45 (15.7) | 23 (8.0) | 35 (12.2) | 2 (0.7%) | NR | NR | NR | 4 (1.4) | NR | 19 (6.6) | 58 |
| SUSTAIN JAPAN 'SITA' | |||||||||||||
| S.c. semaglutide 0.5 mg | 77 (74.8) | 0 | (10.7) | (6.8%) | 0 | 0 | 1 (1.0) | 0 | 4 (3.9) | NR | 3 (2.9) | NR | |
| S.c. semaglutide 1 mg | 73 (71.6) | 1 (1.0) | (12.7) | (8.8%) | 0 | 0 | 3 (2.9) | 0 | 2 (1.9) | NR | 11 (10.8) | NR | |
| Sitagliptin 100 mg | 68 (66.0) | 0 | 0 | (1.9%) | 0 | 1 (1.0) | 0 | 0 | 4 (3.9) | NR | 2 (1.9) | NR | |
| SUSTAIN JAPAN 'INDIVIDUAL' | |||||||||||||
| S.c. semaglutide 0.5 mg | 206 (86.2) | 3 (1.3) | 29 (12.1) | 13 (5.4) | 24 (10.0) | 0 | 0 | 4 (1.7%) | 0 | 11 (4.6) | NR | 14 (5.9) | NR |
| S.c. semaglutide 1 mg | 212 (88) | 6 (2.5) | 46 (19.1) | 14 (5.8) | 38 (15.8) | 0 | 0 | 2 (0.8%) | 0 | 16 (6.6) | NR | 26 (10.8) | NR |
| Additional OAD (investigators discretion) | 86 (71.7) | 2 (1.7) | 1 (0.8) | 2 (1.7) | 8 (6.7) | 0 | 0 | 0 | 0 | 6 (5.0) | NR | 4 (3.3) | NR |
| SUSTAIN China | |||||||||||||
| S.c. semaglutide 0.5 mg | 209 (72.8%) | 2 (0.7%) | 22 (7.7%) | 14 (4.9%) | 58 (20.2%) | 0 | 0 | NR | NR | 19 (6.6%) | NR | 17 (5.9%) | 59 |
| S.c. semaglutide 1 mg | 216 (74,5%) | 6 (2.1%) | 39 (13.4%) | 19 (6.6%) | 49 (16.9%) | 1 (0.3%) | 0 | NR | NR | 14 (4.8%) | NR | 31 (10.7%) | 68 |
| Sitagliptin 100 mg | 199 (68,6%) | 4 (1.4%) | 5 (1.7%) | 3 (1.0%) | 20 (6.9%) | 0 | 0 | NR | NR | 10 (3.4%) | NR | 6 (2.1%) | 17 |
Adverse effects and safety risks in phase 3 trials (10–32).
AE, adverse event; ER, extended release; NR, not reported; OAD, oral antidiabetic drug; s.c. subcutaneous.
An independent external adjudication committee (EAC) validated prespecified categories of adverse events (including deaths, selected cardiovascular events, malignant neoplasms, thyroid diseases [malignant thyroid neoplasms and C-cell hyperplasia], acute kidney injury, acute pancreatitis, and lactic acidosis) except in SUSTAIN 10 where there was no adjudication.
*An episode that was severe according to the ADA classification (requires assistance of another person to actively administer carbohydrate, glucagon, or other corrective action) or an episode with confirmed blood glucose value <56 mg/dL and symptoms consistent with hypoglycemia.
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
Publisher’s Note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Summary
Keywords
glucagon-like peptide-1 receptor agonist (GLP-1RA), oral, subcutaneous, semaglutide, type 2 diabetes, safety
Citation
Smits MM and Van Raalte DH (2021) Corrigendum: Safety of Semaglutide. Front. Endocrinol. 12:786732. doi: 10.3389/fendo.2021.786732
Received
30 September 2021
Accepted
15 October 2021
Published
10 November 2021
Volume
12 - 2021
Edited by
Francesco Giorgino, University of Bari Aldo Moro, Italy
Reviewed by
Stephen Bain, Swansea University, United Kingdom
Updates
Copyright
© 2021 Smits and Van Raalte.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Daniël H. Van Raalte, d.vanraalte@amsterdamumc.nl
This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.