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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · §4

Exenatide — safety

Adverse events as reported, contraindications, warnings, and an explicit statement of what the safety evidence does not establish.

Document identifier
CEI-MN-009/4
Series
Compound monograph
Version
3.2
Published
17 Dec 2024
Last reviewed
17 Apr 2026
Next review
17 Apr 2028
Identifier
10.71829/cei.mono.9
Certainty
High
Cycle
2024 Q4

§4Safety

§4.1Adverse events reported in controlled trials

Table 4. Adverse events for Exenatide as reported in the trial safety tables the Institute holds. Percentages are of randomised participants in the stated trial and arm.

EventActive, %Comparator, %Difference, ppSource
Nausea44.018.0+26.0AMIGO pooled (immediate release)
Vomiting13.04.0+9.0AMIGO pooled
Diarrhoea13.06.0+7.0AMIGO pooled
Injection-site noduleA characteristic finding with the microsphere extended-release product, reported in up to 17 % and generally resolving over weeks to months
Acute pancreatitis0.20.1+0.1EXSCEL
Antibody formationHigher than for human-sequence analogues, reflecting the non-human origin; high-titre antibodies attenuate efficacy in a minority
Discontinuation for adverse events8.03.0+5.0AMIGO pooled
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.
Gastrointestinal adverse eventsProportion of participants reaching each categorical response threshold, by arm.EventActiveComparatorNausea44.0 %18.0 %Vomiting13.0 %4.0 %Diarrhoea13.0 %6.0 %
Figure 4. Gastrointestinal adverse events for Exenatide as reported in the contributing safety tables. Incidences of this kind are dose- and titration-rate-dependent and attenuate with continued exposure in most but not all participants.

§4.2Contraindications

  • Severe renal impairment or end-stage renal disease (eGFR below 30 mL/min/1.73 m²)
  • Personal or family history of medullary thyroid carcinoma (extended-release product)
  • Known hypersensitivity

§4.3Warnings and precautions

  • Boxed warning for thyroid C-cell tumours applies to the extended-release presentation
  • Acute pancreatitis
  • Renal impairment and reports of acute renal failure
  • Hypoglycaemia with secretagogues
  • Immunogenicity with efficacy attenuation at high antibody titre
  • Injection-site nodules with the microsphere product

§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.

  1. Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917 · PMID 28910237
  2. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0 · PMID 19515413

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.

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