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Catalyst

knowpeptidestirzepatide

Specimen peptide organic compound

Tirzepatide

Prescription medicine in the US

FDA boxed warning: thyroid C-cell tumors

fig. 1Tirzepatide · findings by direction and evidence strength
Formula
C225H348N48O68
Molar mass
4813.527 g/mol
ChEBI
CHEBI:194186
InChIKey
BTSOGEDATSQOAF-SMAAHMJQSA-N

↓ lowered 10 findings in 6 endpoints · – no difference found 2 in 2

Strongest evidence
Moderate

Tirzepatide caused thyroid C-cell tumors in rats at exposures relevant to clinical use, more often at higher doses and with longer treatment. Whether it causes them in humans, including medullary thyroid carcinoma (MTC), is not known, because the relevance of the rat tumors to humans has not been determined. It must not be used by anyone who has had MTC, anyone with a family history of MTC, or anyone with multiple endocrine neoplasia type 2 (MEN 2). The label tells prescribers to tell patients about the possible risk of MTC and its symptoms: a lump in the neck, trouble swallowing, shortness of breath, or lasting hoarseness. Routine calcitonin blood tests and thyroid ultrasound are of uncertain value for finding MTC early in people taking it.

FDA labels on DailyMed, each with this warning: type 2 diabetes, effective 2026-08-27 · weight reduction and sleep apnea, effective 2026-08-28

01 · the evidence, ordered

What the evidence says

Strong
0
Moderate
12
Limited
0
Very limited
0
Insufficient
0

How to read these marks

Fig. 2 Tirzepatide CHEBI:194186 8 endpoints 12 findings
×1.60
Labels
PeptideInspector

Tirzepatide

Most findings

  • Body mass×4
  • Body mass index×2
  • All-cause mortality×1
  • Fasting blood glucose×1
Show the remaining 4Show the first 4
  • Glycated haemoglobin (HbA1c)×1
  • Serious adverse event incidence×1
  • Systolic blood pressure×1
  • Total cholesterol (TC)×1

36 compounds on the outer ring, not drawn

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  1. Body mass
  2. Body mass index
  3. All-cause mortality
  4. Fasting blood glucose
  5. Glycated haemoglobin (HbA1c)
  6. Serious adverse event incidence
  7. Systolic blood pressure
  8. Total cholesterol (TC)
fig. 3 · 8 endpoints · 12 findingsno endpoint contested

02 · findings

What tirzepatide moved, and by how much

  • MD mean difference · RR risk ratio. Brackets: the interval as reported.
  • Dose studied: as its paper gave it.
  • Evidence strength: computed from the study. How it is computed
  • Industry funding: named on its row.
Direction

12 shown

  1. Body mass indexMoved: lowersEffect, as reportedMD−5.89[−8.97 to −2.81]Evidence: Moderatereplicated ×1Paper: PMID 405100202025
    Who
    Adults with overweight or obesity without diabetes, six placebo-controlled randomised trials
    Dose studied
    5, 10 or 15 mg or maximum tolerated dose, once weekly

    Additionally, once‐weekly tirzepatide resulted in decreases in BMI and waist circumference, with MDs of −5.89 kg/m2 (95% CI: −8.97 to −2.81, p = 0.0002) (Figure S1A) and −12.31 cm (95% CI: −13.93 to −10.68, p < 0.0001) (Figure S1B), respectively.”

    Quoted verbatim from Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.meta-analysisPermalink
  2. Serious adverse event incidenceMoved: no difference foundEffect, as reportedRR0.93[0.76 to 1.13]Evidence: ModeratePaper: PMID 405100202025
    Who
    Adults with overweight or obesity without diabetes, six placebo-controlled randomised trials
    Dose studied
    5, 10 or 15 mg or maximum tolerated dose, once weekly

    Despite the side effects associated with tirzepatide, the RR for serious adverse events with once‐weekly tirzepatide compared with placebo was 0.93 (95% CI: 0.76–1.13, p = 0.45), which was not statistically significant.”

    Quoted verbatim from Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.meta-analysisPermalink
  3. All-cause mortalityMoved: no difference foundEffect, as reportedRR0.65[0.28 to 1.51]Evidence: ModeratePaper: PMID 405100202025
    Who
    Adults with overweight or obesity without diabetes, six placebo-controlled randomised trials of 18 to 88 weeks
    Dose studied
    5, 10 or 15 mg or maximum tolerated dose, once weekly

    Similarly, the RR for mortality showed no significant difference between tirzepatide and placebo (RR: 0.65, 95% CI: 0.28–1.51, p = 0.32).”

    Quoted verbatim from Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.meta-analysisPermalink
  4. Body mass indexMoved: lowersEffect, as reportedMD−7.21[−8.79 to −5.63]Evidence: Moderatereplicated ×1Paper: PMID 424872132026
    Who
    Adults with obesity or overweight without diabetes, pooled across SURMOUNT placebo-controlled trials
    Dose studied
    15 mg or maximum tolerated dose, once weekly

    Tirzepatide 15 mg/MTD produced greater reductions in BMI (MD −7.21 kg/m2; 95% CI −8.79 to −5.63; p < 0.00001; I 2 = 96%) and waist circumference (MD −14.27 cm; 95% CI −15.43 to −13.10; p < 0.00001; I 2 = 23%) versus placebo.”

    Quoted verbatim from Comparative Efficacy and Safety of Tirzepatide in Asian and Non-Asian Adults With Obesity Without Diabetes: A Systematic Review and Meta-Analysis.meta-analysisPermalink
  5. Body massMoved: lowersEffect, as reportedMD−16.32[−18.35 to −14.29]Evidence: Moderatereplicated ×3Paper: PMID 405100202025
    Who
    Adults with overweight or obesity without diabetes, six placebo-controlled randomised trials of 18 to 88 weeks (five phase 3 SURMOUNT trials and one phase 1 trial)
    Dose studied
    5, 10 or 15 mg or maximum tolerated dose, once weekly

    Compared with placebo, once‐weekly tirzepatide led to a substantial decrease in the percentage change in body weight, with an MD of −16.32% and a 95% CI of −18.35 to −14.29 (p < 0.0001).”

    Quoted verbatim from Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.meta-analysisPermalink
  6. Body massMoved: lowersEvidence: Moderatereplicated ×3Paper: PMID 407473022025
    Who
    Adults with obesity or type 2 diabetes in placebo-controlled phase 1 to 3 trials, pooled across 5, 10 and 15 mg doses
    Dose studied
    5, 10 or 15 mg once weekly

    Pooled analysis demonstrated a reduction in body weight in patients receiving tirzepatide comparing with placebo (WMD=-10.80, 95%CI:-10.80 to -9.99, p < 0.00001), indicating a substantial effect of the treatment.”

    Quoted verbatim from Efficacy and safety of tirzepatide for weight loss in patients with obesity or type 2 diabetes: a systematic review and meta-analysis.meta-analysisPermalink
  7. Body massMoved: lowersEvidence: Moderatereplicated ×3Paper: PMID 424872132026
    Who
    Adults with obesity or overweight without diabetes, pooled across five phase 3 SURMOUNT placebo-controlled trials (six comparisons, N = 4022); percentage change in body weight
    Dose studied
    15 mg or maximum tolerated dose, once weekly

    Tirzepatide 15 mg/MTD produced an 18.04% greater reduction in body weight versus placebo (95% CI −19.86 to −16.22; p < 0.00001; I 2 = 77%).”

    Quoted verbatim from Comparative Efficacy and Safety of Tirzepatide in Asian and Non-Asian Adults With Obesity Without Diabetes: A Systematic Review and Meta-Analysis.meta-analysisPermalink
  8. Systolic blood pressureMoved: lowersEvidence: ModeratePaper: PMID 388504402024Industry funded
    Who
    Adults with or without type 2 diabetes in placebo-controlled trials, 12 to 72 weeks; all three doses
    Dose studied
    5, 10 and 15 mg once weekly

    As shown in Figure S6 and Table S3, all tirzepatide doses significantly reduced systolic blood pressure (SBP) compared to placebo.”

    Quoted verbatim from Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.meta-analysisPermalink
  9. Glycated haemoglobin (HbA1c)Moved: lowersEvidence: ModeratePaper: PMID 388504402024Industry funded
    Who
    Adults with or without type 2 diabetes in placebo-controlled trials, 12 to 72 weeks; all three doses
    Dose studied
    5, 10 and 15 mg once weekly

    All three tirzepatide doses were associated with a significant decrease in HbA1c levels compared to placebo (Figure S8 and Table S3).”

    Quoted verbatim from Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.meta-analysisPermalink
  10. Fasting blood glucoseMoved: lowersEvidence: ModeratePaper: PMID 388504402024Industry funded
    Who
    Adults with or without type 2 diabetes in placebo-controlled trials, 12 to 72 weeks; all three doses
    Dose studied
    5, 10 and 15 mg once weekly

    As shown in Figure S9 and Table S3, all tirzepatide doses resulted in a significant reduction in FPG levels compared to placebo.”

    Quoted verbatim from Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.meta-analysisPermalink
  11. Body massMoved: lowersEvidence: Moderatereplicated ×3Paper: PMID 388504402024Industry funded
    Who
    Adults with or without type 2 diabetes in seven placebo-controlled trials, 12 to 72 weeks; all three doses
    Dose studied
    5, 10 and 15 mg once weekly

    The pooled data analysis showed substantial weight reduction in all three tirzepatide doses compared to the placebo group.”

    Quoted verbatim from Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.meta-analysisPermalink
  12. Total cholesterol (TC)Moved: lowersEvidence: ModeratePaper: PMID 388504402024Industry funded
    Who
    Adults with or without type 2 diabetes in placebo-controlled trials, 12 to 72 weeks; all three doses
    Dose studied
    5, 10 and 15 mg once weekly

    All three doses of tirzepatide significantly decreased TC: −0.25 mmol/L(95% CI:−0.34, −0.15; P <0.00001, high certainty) for 5 mg, −0.30 mmol/L(95% CI:−0.40, −0.20;P <0.00001, high certainty) for 10 mg, and −0.37 mmol/L(95% CI:−0.49, −0.24; P < 0.00001, moderate certainty) for 15 mg.”

    Quoted verbatim from Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.meta-analysisPermalink

No dose is advised.

  • MD mean difference · RR risk ratio. Brackets: the interval as reported.
  • Dose studied: as its paper gave it.
  • Evidence strength: computed from the study. How it is computed
  • Industry funding: named on its row.

03 · identity

Structure

Charge
0
2D depiction
None stored
SMILES
CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)C(C)(C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1ccc(O)cc1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O

04 · the record

Sources

301

papers screened for tirzepatide

admitted
6
read and discarded
64
not read yet
231

The screening record, every paper and why

Documented interactions
None reported

Sources cited

4 papers · 12 findings

2 admitted at screening, no finding yet

Show every paper citedHide the papers cited
617Endpoints measured, not recorded as findingsEvery row, on one page
321Papers indexed under tirzepatide