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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

Tirzepatide — safety

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

Document identifier
CEI-MN-003/4
Series
Compound monograph
Version
4.2
Published
16 Jan 2024
Last reviewed
16 Jan 2025
Next review
16 Jan 2027
Identifier
10.71829/cei.mono.3
Certainty
High
Cycle
2024 Q1

§4Safety

§4.1Adverse events reported in controlled trials

Table 4. Adverse events for Tirzepatide 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
Nausea29.09.5+19.5SURMOUNT-1 (15 mg, 72 weeks)
Diarrhoea23.47.3+16.1SURMOUNT-1
Constipation11.75.8+5.9SURMOUNT-1
Vomiting12.82.6+10.2SURMOUNT-1
Dyspepsia9.12.9+6.2SURMOUNT-1
Injection-site reaction5.60.9+4.7SURMOUNT-1
Alopecia5.41.0+4.4SURMOUNT-1
Cholelithiasis1.60.4+1.2SURMOUNT-1
Acute pancreatitis0.20.1+0.1SURPASS programme pooled
Discontinuation for adverse events4.32.6+1.7SURMOUNT-1
Serious adverse events6.36.2+0.1SURMOUNT-1
Hypoglycaemia (<54 mg/dL)0.20.20.0SURMOUNT-1 (non-diabetic population)
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.EventActiveComparatorNausea29.0 %9.5 %Diarrhoea23.4 %7.3 %Constipation11.7 %5.8 %Vomiting12.8 %2.6 %Dyspepsia9.1 %2.9 %
Figure 4. Gastrointestinal adverse events for Tirzepatide 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

  • Personal or family history of medullary thyroid carcinoma
  • Multiple endocrine neoplasia syndrome type 2
  • Known hypersensitivity to tirzepatide or any excipient
  • Pregnancy

§4.3Warnings and precautions

  • Boxed warning for thyroid C-cell tumours based on rodent data
  • Acute pancreatitis
  • Acute gallbladder disease
  • Hypoglycaemia with insulin or secretagogues
  • Diabetic retinopathy in participants with pre-existing retinopathy
  • Delayed gastric emptying with anaesthetic implications
  • Reduced efficacy of combined oral contraceptives after initiation and dose escalation — a non-oral method or barrier method is advised for four weeks after each escalation
  • Acute kidney injury from volume depletion

§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. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine 2022;387(3):205–216. doi:10.1056/NEJMoa2206038 · PMID 35658024
  2. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2023;402(10402):613–626. doi:10.1016/S0140-6736(23)01200-X · PMID 37385275

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