Tirzepatide

AApproved (Rx)MounjaroZepbounddual GIP/GLP-1 agonist
In one paragraphTirzepatide is a once-weekly peptide that activates both GIP and GLP-1 receptors. It is approved for type 2 diabetes, weight management and obstructive sleep apnoea, and in the only direct head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks) with a similar side-effect profile. It is a prescription medicine; versions sold outside that channel are unlicensed.
Overall gradeA Established
Human trials15+ RCTs
Outcomes graded5
Last reviewed2 September 2026
EvidenceWhat it isHow it worksUnknownsRegulationQuestionsReferences

What the human research shows

The best-evidenced of the newer peptides: a full phase 3 programme in obesity and diabetes, a direct comparison against semaglutide, and an approval in sleep apnoea. The side-effect profile is the familiar GLP-1 one — gut symptoms during dose escalation — and it is well quantified.

OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Body weightAEstablishedLarge10+ RCTsSURMOUNT-1: −20.9% at 72 weeks on 15 mg vs −3.1% placebo in 2,539 adults. SURMOUNT-5 head-to-head: −20.2% vs −13.7% on semaglutide at 72 weeks.12
Blood glucose (HbA1c)AEstablishedLarge5 SURPASS RCTsSURPASS-2: HbA1c reductions of 2.0–2.3 points vs 1.9 on semaglutide 1 mg in type 2 diabetes.3
Obstructive sleep apnoeaAEstablishedModerate2 RCTsSURMOUNT-OSA: apnoea–hypopnoea index fell by roughly 25–30 events per hour vs 5–6 on placebo; basis of the 2024 approval.4
Cardiovascular eventsBProbableSmall1 outcomes RCT (2025)SURPASS-CVOT reported tirzepatide non-inferior to dulaglutide on major adverse cardiovascular events in type 2 diabetes; superiority over an active GLP-1 comparator was not shown.5
GI side effectsadverseAEstablishedLargeAll trialsNausea, diarrhoea and vomiting, mostly during dose escalation. In SURMOUNT-5, GI-related discontinuation was 2.7% vs 5.6% on semaglutide.12
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 2 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

Tirzepatide is a 39-amino-acid peptide built on the GIP hormone backbone and modified so that it also activates the GLP-1 receptor and lasts about five days in the body. Eli Lilly launched it as Mounjaro for type 2 diabetes in 2022 and as Zepbound for weight management in 2023.

It is the drug that turned the semaglutide moment into a category: the first to show that adding a second gut-hormone receptor produces meaningfully more weight loss, and the first to be tested against semaglutide directly rather than by cross-trial comparison.

How it is thought to work

Like semaglutide it activates GLP-1 receptors — more insulin when glucose is high, slower stomach emptying, less appetite. The GIP component appears to add to the appetite effect and to improve how the body handles fat and insulin, and may temper nausea somewhat; the mechanism of that second part is still being worked out.

What is still unknown

  • Whether the cardiovascular benefit matches or exceeds semaglutide's; the outcomes trial used dulaglutide, not placebo, as comparator.
  • Weight regain after stopping — the withdrawal study (SURMOUNT-4) shows substantial regain, as with semaglutide.
  • Long-term effects of the lean-mass component of weight loss.

Regulatory status

European Union
Approved, prescription-only

Mounjaro is authorised by the EMA for type 2 diabetes and weight management.

United States
Approved, prescription-only

Mounjaro (diabetes), Zepbound (obesity, sleep apnoea). Compounded copies were permitted during shortage and are now restricted.

United Kingdom
Approved, prescription-only

NHS rollout for obesity began in 2025 under eligibility criteria.

Sweden
Approved, prescription-only

Subsidy differs between diabetes and weight-management use.

Questions people actually ask

Is tirzepatide better than semaglutide for weight loss?
On the only head-to-head trial, yes: 20.2% versus 13.7% average loss at 72 weeks in 751 adults, with fewer people stopping for gut side effects on tirzepatide. Individual response varies a great deal.
Is tirzepatide a peptide?
Yes — a 39-amino-acid synthetic peptide based on the GIP hormone, modified to also activate GLP-1 receptors and to last about five days.
What are the main side effects?
Nausea, diarrhoea, vomiting and constipation, mostly while the dose is being increased. Rarer but serious: pancreatitis and gallbladder problems. It carries the same thyroid C-cell tumour warning as other GLP-1 drugs, based on rodent findings.
Does the weight come back after stopping?
Largely. In SURMOUNT-4, people switched to placebo after 36 weeks regained about half of what they had lost within a year, while those who continued kept losing.

References

  1. 1
    Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).N Engl J Med, 2022;387:205–2162,539 adults; −20.9% at 72 weeks on 15 mg.
  2. 2
    Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).N Engl J Med, 2025;393(1):26–36751 adults, 72 weeks; −20.2% vs −13.7%; waist −18.4 cm vs −13.0 cm.
  3. 3
    Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).N Engl J Med, 2021;385:503–5151,879 adults; HbA1c and weight vs semaglutide 1 mg.
  4. 4
    Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA).N Engl J Med, 2024;391:1193–1205Two trials, 469 adults; basis of the sleep-apnoea approval.
  5. 5
    Eli Lilly. SURPASS-CVOT topline: tirzepatide vs dulaglutide on cardiovascular outcomes in type 2 diabetes.Press release, 2025; full publication pending at time of reviewNon-inferiority met; graded B until peer-reviewed.

Change log

  • 2026-09-02Full page. Added HbA1c, sleep-apnoea and cardiovascular rows; SURMOUNT-5 head-to-head figures; FAQ and regional status.
  • 2026-09-01Initial publication.