A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Substantial weight loss (“weight-loss shot”)

    Proven benefit

    Energy & metabolism · Patients: obesity or overweight with a comorbidity, without diabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    SURMOUNT-1 (2539 participants, 72 weeks): −15.0 to −20.9% versus −3.1% with placebo [5]. After the switch to placebo, a large part returned [7]. Funded by Eli Lilly or with Lilly employees as authors [5][7]; no efficacy study in people of normal weight.

  • Works more strongly than semaglutide

    Proven benefit

    Energy & metabolism · Patients: obesity without diabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    SURMOUNT-5 (751 participants, 72 weeks): −20.2% versus −13.7%; open-label, not blinded, funded by Eli Lilly [6]. In type 2 diabetes, HbA1c lowered more; this study was also funded by Eli Lilly [4].

  • Protects heart and vessels

    Only proven in patients

    Heart & blood vessels · Patients: heart failure with preserved ejection fraction and obesity, or type 2 diabetes with vascular disease · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    Fewer worsening events of heart failure (hazard ratio 0.62 for the combined endpoint), cardiovascular death not less frequent [11]; noninferior, not superior to dulaglutide [12]. No placebo-controlled endpoint study on myocardial infarction and stroke in obesity without diabetes was examined. Both studies funded by Eli Lilly [11][12].

  • Helps against sleep apnea

    Only proven in patients

    Sleep · Patients: moderate to severe obstructive sleep apnea and obesity · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    Two RCTs over 52 weeks: apnea-hypopnea index lowered by 20.0 and 23.8 events per hour more than with placebo [10]. Funded by Eli Lilly [10].

  • Prevents type 2 diabetes

    Only proven in patients

    Energy & metabolism · Patients: obesity with prediabetes · Human, randomised manufacturer-fundedAccording to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

    After 176 weeks, 1.3% new diabetes cases versus 13.3% with placebo; 17 weeks after discontinuation 2.4% versus 13.7% [8]. Funded by Eli Lilly [8].

manufacturer-funded: According to their funding or competing-interest statements, all studies behind this result were paid for, wholly or in part, by the maker of the product or compound, or list employees of the maker among their authors. Manufacturer-funded studies on average come out more favourably for the product.

Mechanism of action

Evidence map: Tirzepatide

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Tirzepatide is a fatty acid-modified peptide that binds to two gut hormone receptors: to the GIP receptor about as strongly as endogenous GIP (Ki 0.135 nM) and to the GLP-1 receptor about five times more weakly than GLP-1 (Ki 4.23 nM) [1]. The half-life in humans is about 5 days (116.7 hours), and the highest levels occur 24 to 48 hours after the injection [1]. An analysis of receptor occupancy at the clinically used levels shows an imbalance in favor of the GIP receptor; at the GLP-1 receptor, tirzepatide favors cAMP generation over β-arrestin recruitment and causes the receptor to be internalized less often (cell and islet experiments) [2]. In mice, it lowered weight and food intake more than a pure GLP-1 agonist [1].

In type 2 diabetes, tirzepatide improved insulin secretion and insulin sensitivity more than semaglutide and lowered glucagon in a randomized mechanistic study [3]. In the pivotal study SURPASS-2 with 1879 patients, the long-term marker HbA1c fell by 2.0 to 2.3 percentage points versus 1.9 with semaglutide [4]. In SURMOUNT-1 with 2539 adults with obesity without diabetes, participants lost 15.0 to 20.9% depending on dose level in 72 weeks, versus 3.1% with placebo [5]; in the open-label head-to-head comparison SURMOUNT-5, the figures were 20.2% versus 13.7% with semaglutide [6]. Those who switched to placebo after 36 weeks regained 14.0% in the following year [7]. In obesity with prediabetes, the proportion of new type 2 diabetes cases fell from 13.3% to 1.3% over three years [8]. As with other incretin drugs, part of the weight loss is accounted for by fat-free mass, on average 28% [9].

In follow-up studies in comorbidities of obesity, tirzepatide reduced the number of breathing interruptions in obstructive sleep apnea by 20 to 24 events per hour more than placebo [10], and in heart failure with preserved ejection fraction it reduced the rate of cardiovascular death and worsening of heart failure (hazard ratio 0.62), mainly through fewer worsening events [11]. In type 2 diabetes with vascular disease, tirzepatide was noninferior but not significantly superior to the GLP-1 agonist dulaglutide for major cardiovascular events [12]. Eli Lilly funded all of these studies.

Like GLP-1 agonists, tirzepatide delays gastric emptying after the first dose; the effect waned with repeated administration [13]. In mice, GLP-1 agonists trigger thyroid C-cell proliferation via the GLP-1 receptor [14]. In the US adverse event reporting database, contaminations, manufacturing errors and hospital admissions were reported more often for compounded GLP-1 products, including tirzepatide, than for original products [16].

Targets

TargetTypeActionKey dataEvidence
GIP receptorReceptorAgonistKi 0.135 nM, similar to native GIP (laboratory) Laboratory[1][2]
GLP-1 receptorReceptorAgonistKi 4.23 nM, about 5-fold weaker than GLP-1; favors cAMP over β-arrestin (laboratory) Laboratory[1][2]
GLP-1 receptor on thyroid C cells (class effect)ReceptorAgonistC-cell hyperplasia in mice with, not without the receptor; not studied with tirzepatide Animal study[14]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismmodulated · Large weight loss (RCT); food intake lowered in mice[1][5]
  • Insulin · glucosemodulated · Insulin secretion and sensitivity improved, glucagon lowered; HbA1c lowered more than with semaglutide (RCT)[3][4]
  • Inflammation · oxidative↓ · hsCRP lowered in sleep apnea and obesity (RCT)[10]
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Subcutaneous (under the skin) · Prefilled pen or vial (weekly injection)

    Highest levels after 24–48 hours, half-life about 5 days, dose-proportional pharmacokinetics [1]. Absolute bioavailability not verified here.

    Human, randomised

  • Subcutaneous (under the skin) · compounded products

    In US reporting data 2018–2024, more reports of contamination, manufacturing errors and hospital admissions for compounded GLP-1 products than for original products; reporting data do not allow a frequency estimate [16].

    Human, non-randomised

Human studies

  • SURMOUNT-1: weight reduction

    RCT, double-blind, placebo-controlled · Patients: obesity or overweight with a comorbidity, without diabetes · n = 2539 · 72 weeks

    Measured: Weight change in %

    Result: −15.0 to −20.9% versus −3.1%; discontinuation because of side effects 4.3–7.1% versus 2.6%.[5]

    Human, randomised

  • SURMOUNT-5: comparison with semaglutide

    RCT, open-label, active control · Patients: obesity without diabetes · n = 751 · 72 weeks

    Measured: Weight change in %

    Result: −20.2% versus −13.7%; waist circumference −18.4 cm versus −13.0 cm.[6]

    Human, randomised

  • SURMOUNT-4: discontinuation after 36 weeks

    randomized withdrawal study, double-blind · Patients: obesity or overweight with a comorbidity, without diabetes · n = 670 · 36 weeks open-label, then 52 weeks

    Measured: Weight change from week 36

    Result: Continued treatment −5.5%, placebo +14.0%.[7]

    Human, randomised

  • SURPASS-2: type 2 diabetes, comparison with semaglutide

    RCT, open-label, active control · Patients: type 2 diabetes · n = 1879 · 40 weeks

    Measured: HbA1c

    Result: −2.01 to −2.30 versus −1.86 percentage points; serious adverse events 5–7% versus 3%.[4]

    Human, randomised

  • SUMMIT: heart failure with preserved ejection fraction

    RCT, double-blind, placebo-controlled · Patients: heart failure with preserved ejection fraction and obesity · n = 731 · median 104 weeks

    Measured: cardiovascular death or worsening of heart failure; KCCQ-CSS

    Result: Hazard ratio 0.62; cardiovascular death 2.2% versus 1.4% (not significant); quality of life better.[11]

    Human, randomised

  • SURPASS-CVOT: comparison with dulaglutide

    RCT, double-blind, active control, noninferiority · Patients: type 2 diabetes with vascular disease · n = 13299 · event-driven

    Measured: cardiovascular death, myocardial infarction, stroke

    Result: Hazard ratio 0.92 (95.3% CI 0.83–1.01): noninferior, not superior.[12]

    Human, randomised

  • SURMOUNT-OSA: sleep apnea

    two RCTs, double-blind, placebo-controlled · Patients: obstructive sleep apnea and obesity · 52 weeks

    Measured: Apnea-hypopnea index

    Result: −20.0 and −23.8 events per hour versus placebo.[10]

    Human, randomised

  • Islet cell function

    RCT, double-blind, phase 1, with a semaglutide arm · Patients: type 2 diabetes · n = 117 · 28 weeks

    Measured: Clamp disposition index, insulin secretion, insulin sensitivity

    Result: Greater improvement than with placebo and semaglutide.[3]

    Human, randomised

Risks and warnings

  • Gastrointestinal complaints

    Nausea, diarrhea and vomiting are the most common side effects, mainly in the first weeks of treatment [5][8]; discontinuation because of side effects 4.3–7.1% versus 2.6% with placebo [5].

    Human, randomised

  • Weight regain after discontinuation

    After the switch to placebo, +14.0% in one year [7].

    Human, randomised

  • Loss of fat-free mass

    On average, 28% of the weight loss under incretin drugs was accounted for by muscle-related measures; bodily function not measured [9].

    Human, randomised

  • Delayed gastric emptying

    Marked after the first dose, diminishing with repeated administration; in type 2 diabetes a residual delay remained [13].

    Human, randomised

  • Thyroid C cells (animal finding)

    Class effect of GLP-1 agonists in mice; not tested with tirzepatide here, relevance for humans unclear [14].

    Animal study

  • Compounded and illegal products

    More reports of contamination, preparation errors and hospital admissions for compounded GLP-1 products [16].

    Human, non-randomised

Interactions

  • Oral medicines (gastric emptying): The delayed gastric emptying after the start of therapy can change the absorption of oral medicines; measured only with paracetamol as a marker [13].

Fact check: common claims

  • partly supported

    “Tirzepatide is the strongest weight-loss shot, stronger than Wegovy”

    Stronger than semaglutide in the head-to-head comparison [6], but open-label and manufacturer-funded; newer compounds such as retatrutide are not compared here.

  • refuted

    “The weight stays down even after discontinuation”

    After the switch to placebo, participants regained 14.0% in one year [7].

  • not supported

    “Tirzepatide burns only fat and spares muscle”

    For incretin drugs overall, on average 28% of the weight loss is accounted for by muscle-related measures [9].

  • not supported

    “Tirzepatide acts mainly via the GLP-1 receptor, GIP plays no role”

    At clinical levels, tirzepatide occupies the GIP receptor more strongly [2]; what share GIP has in the weight loss in humans is open.

Pharmacokinetics

Absorption
Subcutaneous; highest levels after 24–48 hours [1].
Half-life
About 5 days (116.7 hours) in humans [1].
Metabolism
Fatty acid chain prolongs the duration of action [1]; degradation pathways not verified here.
Entry into the brain
Not verified in humans.

Legal status

Germany
Also authorized as a medicine in Germany through the central EU authorization [15]; prescription requirement and reimbursement not checked in registers.
EU
Approved by the EMA in type 2 diabetes and for weight reduction [15].
USA
Approved by the FDA in type 2 diabetes and for weight reduction [15].

Related compounds

Semaglutidesame classRetatrutidesame class

Open questions

  • What share does GIP receptor activation have in the weight loss in humans?
  • Does tirzepatide lower myocardial infarction and stroke in obesity without diabetes compared with placebo?
  • How does the loss of fat-free mass affect strength and function?

References

  1. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab. 2018;18:3–14. doi:10.1016/j.molmet.2018.09.009 · PubMed
  2. Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17):e140532. doi:10.1172/jci.insight.140532 · PubMed
  3. Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, et al. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022;10(6):418–29. doi:10.1016/S2213-8587(22)00085-7 · PubMed
  4. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–15. doi:10.1056/NEJMoa2107519 · PubMed
  5. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–16. doi:10.1056/NEJMoa2206038 · PubMed
  6. Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26–36. doi:10.1056/NEJMoa2416394 · PubMed
  7. Aronne LJ, Sattar N, Horn DB, Bays HE, Wharton S, Lin WY, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945 · PubMed
  8. Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, et al. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. 2025;392(10):958–71. doi:10.1056/NEJMoa2410819 · PubMed
  9. Batsis JA, Gavras A, Gross DC, Cheever CR, Da Silva BR, Meira Filho LF, et al. Effect of incretin-based and nonpharmacologic weight loss on body composition: a systematic review. Ann Intern Med. 2026;179(7):996–1013. doi:10.7326/ANNALS-25-00478 · PubMed
  10. Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193–205. doi:10.1056/NEJMoa2404881 · PubMed
  11. Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392(5):427–37. doi:10.1056/NEJMoa2410027 · PubMed
  12. Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409–20. doi:10.1056/NEJMoa2505928 · PubMed
  13. Urva S, Coskun T, Loghin C, Cui X, Beebe E, O'Farrell L, et al. The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists. Diabetes Obes Metab. 2020;22(10):1886–91. doi:10.1111/dom.14110 · PubMed
  14. Madsen LW, Knauf JA, Gotfredsen C, Pilling A, Sjögren I, Andersen S, et al. GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology. 2012;153(3):1538–47. doi:10.1210/en.2011-1864 · PubMed
  15. Sidrak WR, Kalra S, Kalhan A. Approved and emerging hormone-based anti-obesity medications: a review article. Indian J Endocrinol Metab. 2024;28(5):445–60. doi:10.4103/ijem.ijem_442_23 · PubMed
  16. McCall KL, Mastro Dwyer KA, Casey RT, Samana TN, Sulicz EK, Tso SY, et al. Safety analysis of compounded GLP-1 receptor agonists: a pharmacovigilance study using the FDA adverse event reporting system. Expert Opin Drug Saf. 2026;25(3):581–8. doi:10.1080/14740338.2025.2499670 · PubMed
How this profile was checked

Last reviewed: 2026-10-25. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-25); translation checked on 2026-10-26.

Checked

  • All abstracts read via PubMed (XML), DOIs and PMIDs reconciled with tools/pruefe_profile.py.
  • In the full text (PMC6308032): Ki GIPR 0.135 nM, GLP-1R 4.23 nM, about 5-fold weaker than GLP-1, t½ ≈ 5 days (116.7 h), Tmax 24–48 h [1].
  • Key figures checked against abstracts: imbalance in favor of GIPR, cAMP over β-arrestin [2]; n = 117, disposition index, glucagon [3]; n = 1879, HbA1c −2.01 to −2.30 vs. −1.86 [4]; n = 2539, −15.0 to −20.9 vs. −3.1%, discontinuations [5]; n = 751, −20.2 vs. −13.7%, open-label [6]; n = 670, −5.5 vs. +14.0% [7]; 1.3 vs. 13.3%, 2.4 vs. 13.7% [8]; median 28.3% [9]; AHI −20.0/−23.8 [10]; n = 731, HR 0.62, CV death HR 1.58 [11]; n = 13,299, HR 0.92 [12]; gastric emptying [13]; mouse, GLP-1R knockout [14]; FAERS, 707 reports on compounded products [16].
  • In the full text (PMC11642516): tirzepatide approved by the FDA and EMA in type 2 diabetes and for weight reduction [15].
  • Funding: Eli Lilly for [3][4][5][6][7][8][10][11][12]; authors employed by the manufacturer for [1][2][13].
  • ClinicalTrials.gov: 324 entries for “tirzepatide” (October 23, 2026); no entry from the sponsor “Hudson Biotech” found.
  • October 25, 2026, trade names (guideline “Handelsnamen” (trade names), decision of October 25, 2026: evidence from the EPAR, summary of product characteristics, Drugs@FDA or the Article 57 database; US names only if there is no DE/EU name; applied by analogy because tirzepatide is a centrally authorized medicine despite `kategorie` peptide, see `status`): “Zepbound” removed from synonyme. The name was not documented in the profile and is a purely US name: Drugs@FDA queried via openFDA on October 25, 2026, ZEPBOUND under NDA 217806 prescription-only; no entry in the EMA database under Article 57 (Article 57 product data, EMA/518502/2018 Rev. 90, data as of October 9, 2026, retrieved on October 25, 2026). “Mounjaro” stays as the EU name: listed in the same list for the European Union (central authorization, thus also Germany), Iceland, Liechtenstein and Norway; in the EMA medicines export (medicines, retrieved on October 25, 2026) Mounjaro, EMEA/H/C/005620, status “Authorised”. The listing does not document the content of the authorization; status is unchanged.
  • October 26, 2026, precision flags (m004; rules in the guideline under “Number rule and precision flags”, implementation by Claude pending confirmation by Tilman): “Substantial weight loss (‘weight-loss shot’)”: manufacturer-funded – [5] “Supported by Eli Lilly” according to the abstract; [7] authors employed by Eli Lilly according to the conflict-of-interest statement. “Works more strongly than semaglutide”: manufacturer-funded – [4] and [6] “Funded by Eli Lilly” according to the abstract. “Protects heart and vessels”: manufacturer-funded – [11] and [12] “Funded by Eli Lilly” according to the abstract. “Helps against sleep apnea”: manufacturer-funded – [10] “Funded by Eli Lilly” according to the abstract. “Prevents type 2 diabetes”: manufacturer-funded – [8] “Funded by Eli Lilly” according to the abstract. Cross-check October 26, 2026: evidence for the flags (participant numbers, direction, funding) incorporated into the begruendung and rechecked against abstracts or full texts.

Not verified

  • Absolute bioavailability after subcutaneous administration (no primary source found).
  • Biliary tract and pancreatitis risk specifically for tirzepatide not checked (the meta-analysis in the semaglutide profile concerns GLP-1 agonists).
  • German status (prescription requirement, reimbursement) not checked in registers; EMA pages blocked.
  • Doping status not checked.
  • How many participants the two SURMOUNT-OSA studies had together (not stated in the abstract).

No dosages, no sources of supply. This information does not replace medical advice.

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