Tirzepatide — compound monograph
Dual GIP and GLP-1 receptor agonist (acylated). Approved. The Institute assesses 9 outcomes for this compound and grades the strongest at high certainty.
§1Identification and status
§1.1Nomenclature
- Preferred name
- Tirzepatide
- Compound class
- Dual GIP and GLP-1 receptor agonist (acylated)
- Assessment series
- Incretin receptor agonists
- Synonyms and codes
- LY3298176 · tirzepatide (INN) · Mounjaro (trade) · Zepbound (trade)
- Route as evaluated
- Subcutaneous once weekly
§1.2Chemistry
Chemical identifiers are reproduced where they are public. Where a structure has not been published the monograph records not disclosed rather than constructing one.[1]
- CAS registry number
- 2023788-19-2
- Molecular formula
- C225H348N48O68
- Average mass
- 4813.45
- Monoisotopic mass
- 4810.55
- ATC classification
- A10BX16
§1.3Sequence and structural notes
A 39-residue synthetic peptide based on the native GIP sequence, engineered for balanced activity at GIP and GLP-1 receptors. α-Aminoisobutyric acid at positions 2 and 13 confers DPP-4 resistance and modulates receptor selectivity; lysine 20 carries a γ-glutamate spacer, two AEEA units and an eicosanedioic (C20) diacid for albumin binding. The C-terminus is amidated.
§1.4Assessment status
The Institute assesses Tirzepatide across 9 indications and grades the strongest of them at high certainty. Holds a marketing authorisation for at least one indication in at least one jurisdiction.
Table 1. Assessed outcomes for Tirzepatide, ordered by certainty. Each row links to the per-indication evidence extract.
| Indication | Effect as recorded | Certainty | Trials |
|---|---|---|---|
| Obesity and overweight in adults | −20.9 % body weight at 72 weeks with 15 mg versus −3.1 % with placebo (SURMOUNT-1) | High | 5 |
| Obstructive sleep apnoea with obesity | Apnoea–hypopnoea index reduced by 25.3 events/hour versus 5.3 with placebo in participants not using positive airway pressure | High | 2 |
| Type 2 diabetes mellitus | −1.87 to −2.59 % HbA1c across doses and backgrounds; superior to semaglutide 1.0 mg, insulin degludec and insulin glargine | High | 5 |
| Atherosclerotic cardiovascular disease and cardiovascular risk reduction | MACE hazard ratio 0.92 versus dulaglutide 1.5 mg in an active-controlled non-inferiority design | Moderate | 1 |
| Heart failure with preserved ejection fraction and obesity | Composite of cardiovascular death or worsening heart failure hazard ratio 0.62 | Moderate | 1 |
| Prediabetes and progression to type 2 diabetes | Progression to type 2 diabetes at 176 weeks reduced by 94 % in the prediabetes cohort | Moderate | 1 |
| Knee osteoarthritis with obesity | WOMAC pain score improvement exceeding placebo at 68 weeks | Low | 1 |
| Metabolic dysfunction-associated steatohepatitis | Resolution of steatohepatitis without worsening fibrosis in 44–62 % across doses versus 10 % with placebo at 52 weeks | Low | 1 |
| Sarcopenia and lean-mass preservation during weight reduction | Approximately 25 % of total mass lost was lean mass in the body-composition substudy | Low | 1 |
| Effects are reproduced as the contributing trials reported them. Where a confidence interval is held it appears on the per-indication extract rather than in this summary table. | |||
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.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute
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.