Tirzepatide

Mounjaro, Zepbound (brand names of the approved medicine), LY3298176

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Tirzepatide is an approved prescription medicine in most countries, not a research-only compound. This page explains the published science. Use outside a prescription — including compounded or grey-market versions — carries real risks discussed below.

Summary

Class: Dual GIP and GLP-1 receptor agonist; 39-amino-acid synthetic peptide built on the GIP sequence, with a C20 fatty-diacid side chain that binds albumin and extends its action
Mechanism: Activates both of the gut's main incretin receptors: boosts glucose-dependent insulin release, lowers glucagon, slows stomach emptying and strongly reduces appetite, with GIP activity possibly improving fat-tissue handling and tolerability
Routes studied: Subcutaneous once-weekly (approved); oral forms not available
Dose range reported: Approved: 2.5 mg weekly for 4 weeks, then increase by 2.5 mg every 4+ weeks as tolerated to 5, 7.5, 10, 12.5 or 15 mg weekly (maintenance 5–15 mg). Trials used exactly these titrations
Half-life: ~5 days (~120 hours); weekly dosing; steady state after about 4 weeks
Storage: Approved pens/vials: refrigerate; may be kept at room temperature (up to 30 °C) for up to 21 days. Lyophilised compounded product: refrigerate, follow the label
Regulatory status: Approved medicine (US, EU, UK, AU and others; South Africa registered 2025 †)

Doses are as reported in studies or by the community — never recommendations.

1What it is

Tirzepatide is a single molecule that acts on two incretin hormone receptors at once. Incretins are gut hormones released after eating: GLP-1 (the target of semaglutide) and GIP (glucose-dependent insulinotropic polypeptide). For years GIP was thought unhelpful in obesity, but Eli Lilly's team found that a GIP-based peptide engineered to also hit the GLP-1 receptor produced more weight loss and glucose lowering than GLP-1 agonism alone, with fewer gut side effects per unit of effect. The molecule is synthetic; nothing in the body has this sequence.

It was approved for type 2 diabetes in 2022 (Mounjaro) and for chronic weight management in late 2023 (Zepbound in the US; Mounjaro carries the obesity indication in many other markets). In 2024 it was also approved for obstructive sleep apnoea in adults with obesity. It currently produces the largest average weight loss of any approved medicine.

2How it's thought to work

Pancreas. glucose-dependent insulin release and glucagon suppression via both receptors; GIP also directly stimulates insulin release.

Brain. reduced appetite and food reward through GLP-1 receptors in the hypothalamus and brainstem; GIP receptor activation in the brain appears to reduce nausea, which may be why tirzepatide is tolerated at doses that produce more weight loss.

Stomach. slows gastric emptying, particularly early in treatment.

Fat tissue. GIP receptors in adipocytes may improve lipid storage and insulin sensitivity; this is an active research area.

Imbalanced agonism. tirzepatide is a full GIP but a weaker, biased GLP-1 agonist, which may contribute to its profile.

One molecule activates two incretin receptors, GIP and GLP-1: insulin release from the pancreas, effects on fat tissue, and reduced appetite in the brain.Schematic — not to scale

3What the research shows

Weight loss in people with obesity

SURMOUNT-1 (n≈2,539, no diabetes): mean weight change −15.0% (5 mg), −19.5% (10 mg) and −20.9% (15 mg) vs −3.1% placebo at 72 weeks (Jastreboff 2022, NEJM). SURMOUNT-2 in people with type 2 diabetes showed −12.8% to −14.7%. SURMOUNT-3 and -4 covered post-lifestyle and maintenance settings; withdrawal in SURMOUNT-4 led to regain of about half the lost weight within a year (Aronne 2024, JAMA). [1][4]

Head-to-head versus semaglutide

SURMOUNT-5 (n≈751, obesity without diabetes): tirzepatide 15 mg produced −20.2% vs −13.7% with semaglutide 2.4 mg at 72 weeks (Aronne 2025, NEJM). SURPASS-2 in type 2 diabetes showed superior HbA1c and weight reduction vs semaglutide 1 mg (Frías 2021, NEJM). [2][5]

Type 2 diabetes glucose control

SURPASS 1–5: HbA1c reductions of roughly 1.9–2.6 percentage points, superior to insulin degludec and insulin glargine, with a large share of participants reaching HbA1c below 5.7% (Rosenstock 2021, Lancet; Del Prato 2021, Lancet). [3]

Cardiovascular outcomes

SURPASS-CVOT (n≈13,299, type 2 diabetes with established cardiovascular disease): tirzepatide was non-inferior to dulaglutide for major adverse cardiovascular events, with a lower rate of all-cause death reported (2025) †. SURMOUNT-MMO, the obesity outcomes trial, is ongoing.

Obstructive sleep apnoea

SURMOUNT-OSA: apnoea-hypopnoea index reduced by about 25–29 events per hour vs 5–6 with placebo (Malhotra 2024, NEJM), leading to approval for this indication. [6]

Heart failure with preserved ejection fraction

SUMMIT: reduced the composite of heart-failure events and improved symptoms in people with obesity-related HFpEF (Packer 2025, NEJM). [7]

Liver (MASH), diabetes prevention

SYNERGY-NASH Phase 2 showed resolution of MASH without worsening fibrosis in a majority at higher doses (Loomba 2024, NEJM). SURMOUNT-1's 3-year extension showed a ~94% reduction in progression to type 2 diabetes among people with prediabetes (Jastreboff 2025, NEJM). [8]

4Reported side effects and interactions

Literature-reported

Common (literature). nausea (roughly 25–30% at higher doses in SURMOUNT-1), diarrhoea, vomiting, constipation, dyspepsia, abdominal pain, reduced appetite, fatigue, injection-site reactions, hair thinning (reported more often than placebo). Mostly dose-related and during escalation.

Serious / warnings. gallbladder disease; pancreatitis (rare); hypoglycaemia when combined with insulin or sulfonylureas; acute kidney injury secondary to dehydration from GI effects; delayed gastric emptying with aspiration risk under anaesthesia; boxed warning for thyroid C-cell tumours seen in rodents — contraindicated with personal/family history of medullary thyroid carcinoma or MEN2; diabetic retinopathy complications not specifically studied; hypersensitivity reactions including anaphylaxis reported; suicidal ideation signals investigated by regulators with no causal link established.

Muscle mass. lean mass accounts for a substantial fraction of weight lost (around a quarter in body-composition sub-studies); protein intake and resistance training are standard advice.

Compounded and grey-market product risks. unit confusion (mg vs ml vs "units"), unverified salt forms or impurities, mislabelled or underfilled vials, and copies of the discontinued vial-based products. Regulators in the US, UK, EU and Australia have issued warnings, and the US compounding window closed after the shortage was declared resolved.

Interactions. increased hypoglycaemia with insulin or sulfonylureas (doses are usually reduced); slowed absorption of oral medicines; the label specifically advises a back-up method of contraception for 4 weeks after starting and after each dose increase in people using oral contraceptives; not for use in pregnancy.

Markers researchers commonly monitor

Marker	Why it's watched
HbA1c and fasting glucose	primary glycaemic markers; hypoglycaemia risk if combined with insulin or sulfonylureas.
Body weight, waist circumference and body composition (DEXA or bioimpedance)	to track fat versus lean loss.
Lipase/amylase	only if symptoms suggest pancreatitis; routine measurement is not recommended because mild elevations are common and non-specific.
Creatinine/eGFR and electrolytes	dehydration from GI effects can injure kidneys.
Liver enzymes	generally improve; useful if MASH is a concern.
Lipids and blood pressure	typically improve with weight loss.
Heart rate	small sustained increase of a few beats per minute is typical of the class.
Thyroid: calcitonin is not routinely recommended but is sometimes checked at baseline

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5Reconstitution and handling

Approved pens and single-dose vials need no . vials require careful maths: doses are in milligrams, vials often contain 10–60 mg, and the volume per dose is small. Use the calculator and double-check units and the strength on the vial.

Open in calculator, pre-loaded →

6Commonly studied alongside

Semaglutide and dulaglutide (as comparators, not together), basal insulin and metformin (in SURPASS trials), lifestyle interventions. Lilly's follow-on compounds (retatrutide, orforglipron, bimagrumab for lean-mass preservation) are studied separately or in combination trials.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Mounjaro 2022 for type 2 diabetes; Zepbound 2023 for weight management, 2024 for obstructive sleep apnoea). Shortage declared resolved December 2024; compounding of copies no longer permitted except for individual clinical need
European Union	EMA-authorised (Mounjaro) for type 2 diabetes and weight management
United Kingdom	MHRA-licensed; NHS roll-out for obesity began 2025 with eligibility phased by BMI and comorbidity
Australia	TGA-approved (Mounjaro) for type 2 diabetes and weight management; compounding of GLP-1 copies banned from Oct 2024
South Africa	SAHPRA-registered (Mounjaro) 2025 †
Sport (WADA)	Not prohibited (as of review date) †

8Open questions

Lowest effective maintenance dose and whether dose reduction preserves weight loss.
Long-term effects on muscle, bone and gallbladder over many years.
Cardiovascular outcomes in obesity without diabetes (SURMOUNT-MMO) and whether GIP agonism adds to cardiovascular benefit.

9References

1Jastreboff AM et al. (2022). Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. PubMed · DOI
2Frías JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med. PubMed · DOI
3Rosenstock J et al. (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1). Lancet. PubMed · DOI
4Aronne LJ et al. (2024). Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. PubMed · DOI
5Aronne LJ et al. (2025). Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med. PubMed · DOI
6Malhotra A et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). N Engl J Med. PubMed · DOI
7Packer M et al. (2025). Tirzepatide for heart failure with preserved ejection fraction and obesity (SUMMIT). N Engl J Med. PubMed · DOI
8Loomba R et al. (2024). Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis (SYNERGY-NASH). N Engl J Med. PubMed · DOI
9Eli Lilly. Mounjaro / Zepbound prescribing information (current label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

25 Oct 2026Profile published — awaiting medical review

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