Semaglutide — safety
Adverse events as reported, contraindications, warnings, and an explicit statement of what the safety evidence does not establish.
§4Safety
§4.1Adverse events reported in controlled trials
Table 4. Adverse events for Semaglutide as reported in the trial safety tables the Institute holds. Percentages are of randomised participants in the stated trial and arm.
| Event | Active, % | Comparator, % | Difference, pp | Source |
|---|---|---|---|---|
| Nausea | 44.2 | 17.4 | +26.8 | STEP 1 (68 weeks, 2.4 mg) |
| Diarrhoea | 31.5 | 15.9 | +15.6 | STEP 1 |
| Vomiting | 24.8 | 6.6 | +18.2 | STEP 1 |
| Constipation | 23.4 | 9.5 | +13.9 | STEP 1 |
| Dyspepsia | 9.6 | 3.9 | +5.7 | STEP 1 |
| Abdominal pain | 10.0 | 5.6 | +4.4 | STEP 1 |
| Cholelithiasis | 2.6 | 1.2 | +1.4 | STEP 1 |
| Acute pancreatitis | 0.2 | 0.1 | +0.1 | SELECT (mean 39.8 months) |
| Discontinuation for adverse events | 7.0 | 3.1 | +3.9 | STEP 1 |
| Serious adverse events | 9.8 | 6.4 | +3.4 | STEP 1 |
| Acute gallbladder disease | 2.8 | 2.3 | +0.5 | SELECT |
| Alopecia | 1.5 | 0.5 | +1.0 | SELECT |
| A difference column is computed by the Institute from the two reported percentages and is not itself a published figure. Confidence intervals for adverse-event differences are not reported in the contributing trials and are not constructed here. | ||||
§4.2Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
- Known hypersensitivity to semaglutide or any excipient
- Pregnancy (discontinue at least two months before a planned pregnancy given the long half-life)
§4.3Warnings and precautions
- Boxed warning for thyroid C-cell tumours based on rodent carcinogenicity studies; human relevance is not established
- Acute pancreatitis — discontinue if suspected
- Acute gallbladder disease, particularly with rapid weight reduction
- Diabetic retinopathy complications reported in SUSTAIN 6 in participants with pre-existing retinopathy and rapid glycaemic improvement
- Hypoglycaemia when combined with insulin or a sulfonylurea
- Delayed gastric emptying with implications for procedural sedation and general anaesthesia
- Acute kidney injury secondary to volume depletion from gastrointestinal loss
§4.4What this section does not establish
Related assessments: tolerability of incretin receptor agonists · acute pancreatitis · the rodent thyroid C-cell signal.[1,2]
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183 · PMID 33567185
- Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet 2021;397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0 · PMID 33667417
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.