How does Mounjaro work? Tirzepatide, explained.
Mounjaro's active ingredient, tirzepatide, is the first registered medicine that activates two gut-hormone receptors at once: GIP and GLP-1. This explainer covers what that does in the body, what the SURPASS (diabetes) and SURMOUNT (weight and sleep apnoea) trials measured, how the dose builds, what happens after stopping, and who it is registered for in Australia. The figures are trial averages with sources, describing groups of volunteers rather than any one person.
Tirzepatide mimics two gut hormones, GIP and GLP-1. Acting on receptors in the pancreas, gut and brain, it increases insulin release when glucose is high, lowers glucagon, slows stomach emptying (mostly early on) and reduces appetite and food intake. In 72-week trials, adults without diabetes lost an average of 15 to 21 per cent of body weight on 5 to 15 mg versus 3 per cent on placebo; adults with type 2 diabetes saw HbA1c fall by about 2 percentage points over 40 weeks. Gastrointestinal side effects were common, and when the medicine was withdrawn in a randomised trial most of the lost weight returned within a year.
- Registered for type 2 diabetes in adults since 22 December 2022. Source: TGA registration decision.
- Registered for chronic weight management since 9 September 2024, in adults with a BMI of 30 or more, or 27 to under 30 with a weight-related condition. Source: TGA registration decision.
- Registered for moderate to severe obstructive sleep apnoea in adults with obesity since 27 May 2025; the current PI (vA13.0, September 2026) also lists type 2 diabetes from age 10 at 50 kg or more. Sources: TGA registration decision; TGA ARTG entry.
- Not PBS-listed for any indication. The PBAC recommended a type 2 diabetes listing in March 2026; in April 2026 the sponsor declined to proceed and the listing process ceased. Sources: PBS; RACGP newsGP, 28 April 2026.
- Supply and use. Pharmacy compounding of GLP-1 medicines has not been permitted since 1 October 2024 (TGA); about 500,000 Australians used a GLP-1 medicine each month by April 2025 (UNSW, 31 July 2026).
Two receptors, one molecule.
After a meal the gut releases incretin hormones. Two of them, GIP and GLP-1, tell the pancreas to release insulin, signal fullness to the brain and slow the passage of food. Tirzepatide is a laboratory-made chain of amino acids shaped to fit both receptors, attached to a fatty acid that binds it to albumin in the blood, which is what allows once-weekly injection. The PI describes it as "a long-acting GIP and GLP-1 receptor agonist".
Semaglutide (Ozempic, Wegovy) acts on the GLP-1 receptor only; see Mounjaro versus Wegovy.
Four effects the Product Information describes.
More insulin is released when glucose is high and little when it is not. In a clamp study, 15 mg raised first-phase insulin secretion by 466 per cent and lowered fasting glucagon by 28 per cent. That glucose-dependence is why hypoglycaemia is uncommon without insulin or a sulfonylurea.
In the same study, 15 mg improved whole-body insulin sensitivity by 63 per cent. The PI says weight loss contributes, and that the weight lost is mostly fat mass.
Delayed, "with largest delay after the first dose", diminishing over time. This blunts the post-meal glucose rise, adds to early fullness, and is why the PI warns about oral medicine absorption and aspiration under anaesthesia.
Both receptors are present in brain regions that regulate appetite. The PI states that tirzepatide "regulates appetite and decreases food intake", and that reduced intake drives the weight loss.
What the SURPASS and SURMOUNT trials found.
The TGA's assessment rested on two manufacturer-funded programs: SURPASS in type 2 diabetes and SURMOUNT in obesity. All participants also received diet and activity counselling.
| Trial | Who took part | Length | Main result, tirzepatide versus comparator |
|---|---|---|---|
| SURPASS-1 Lancet 2021 | 478 adults with type 2 diabetes on diet and exercise | 40 weeks | HbA1c fell 1.87, 1.89 and 2.07 points on 5, 10 and 15 mg; it rose 0.04 on placebo. |
| SURPASS-2 NEJM 2021 | Adults with type 2 diabetes on metformin | 40 weeks | HbA1c fell 2.01, 2.24 and 2.30 points versus 1.86 on semaglutide 1 mg; serious adverse events 5 to 7 versus 3 per cent. |
| SURMOUNT-1 NEJM 2022 | 2,539 adults with BMI 30 or more (or 27 with a complication), no diabetes | 72 weeks | Weight minus 15.0, 19.5 and 20.9 per cent on 5, 10 and 15 mg versus minus 3.1 on placebo. |
| SURMOUNT-2 Lancet 2023 | 938 adults with type 2 diabetes and obesity or overweight | 72 weeks | Weight minus 12.8 and 14.7 per cent (10 and 15 mg) versus minus 3.2 on placebo. |
| SURMOUNT-OSA NEJM 2024 | Adults with moderate to severe sleep apnoea and obesity | 52 weeks | Breathing interruptions (AHI) fell 25.3 and 29.3 events per hour in two trials, versus 5.3 and 5.5 on placebo. |
Every figure is a group mean from a selected population under study conditions. Trial results are not a forecast for an individual.
How long things take.
The pharmacology starts with the first injection; the dose builds slowly by design. The PI starts at 2.5 mg weekly for 4 weeks, an initiation dose, then 5 mg; further increases are 2.5 mg at a time after at least 4 weeks on the current dose, so reaching 15 mg takes at least 20 weeks (see the Mounjaro doses guide). In the trials, HbA1c was measured at 40 weeks and weight at 72, with average weight still changing at the end. Gastrointestinal effects ran the other way: most frequent during escalation, easing with time (see the Mounjaro side effects guide).
What happens when it is stopped.
SURMOUNT-4 (JAMA 2024) was designed to answer this. After 36 weeks on tirzepatide, during which participants lost an average of 20.9 per cent of body weight, they were randomised to continue or switch to placebo. Over the next 52 weeks the placebo group regained an average of 14.0 per cent while the continuing group lost a further 5.5 per cent; 89.5 per cent of continuers kept at least 80 per cent of their loss, against 16.6 per cent on placebo.
The CMI says not to stop suddenly without consulting your doctor, and that in type 2 diabetes blood sugar may rise. If and when to stop is the prescriber's decision, made with the person taking it.
Who it is registered for.
As of 1 October 2026 the PI lists four indications: adults with insufficiently controlled type 2 diabetes, as an adjunct to diet and exercise; children aged 10 and over weighing 50 kg or more with type 2 diabetes; chronic weight management in adults with a BMI of 30 or more, or 27 to under 30 with a weight-related condition; and moderate to severe obstructive sleep apnoea in adults with obesity.
Meeting a criterion does not make the medicine suitable; that is the prescriber's judgement.
Who should not use it, or needs extra care.
The PI's only contraindication is known hypersensitivity to tirzepatide or any excipient. It is not for type 1 diabetes or diabetic ketoacidosis, not for pregnancy (Category D; stop at least one month before a planned pregnancy), and not studied under 18 for weight or sleep apnoea.
Caution applies with a history of pancreatitis, severe gastrointestinal disease, diabetic retinopathy, heart failure, severe kidney or liver impairment or suicidal thoughts; insulin or sulfonylurea doses may need review; and oral contraceptive users are advised to add a barrier method for 4 weeks after starting and after each dose increase.
Why food still matters.
Every Australian indication is worded as an adjunct to diet and physical activity. A medicine that lowers appetite lowers total food eaten, which is why the PI warns of malnutrition, "including vitamin and mineral deficiency, protein deficiency, and low body weight", and says balanced nutritional support should be considered.
In practice that means a protein food at each meal, fibre from vegetables, fruit and whole grains, and fluids through the day. See what to eat on Mounjaro, the GLP-1 meal plan, the portion guide and the tirzepatide food guide; for the wider picture, GLP-1 medicines in Australia and weight-loss medication in Australia.
How does Mounjaro work for weight loss?
Tirzepatide activates GIP and GLP-1 receptors in brain areas that regulate appetite. The PI says it regulates appetite, decreases food intake and slows stomach emptying, and that the weight lost is mostly fat mass. It is registered as an adjunct to diet and physical activity.
Is Mounjaro the same as Ozempic?
No. Ozempic and Wegovy contain semaglutide, a GLP-1 receptor agonist only; tirzepatide acts on GIP and GLP-1 receptors. In SURPASS-2, tirzepatide lowered HbA1c by 2.01 to 2.30 points over 40 weeks versus 1.86 for semaglutide 1 mg, with more serious adverse events.
How much weight did people lose on Mounjaro in trials?
In SURMOUNT-1 (no diabetes), mean weight change at 72 weeks was minus 15.0, 19.5 and 20.9 per cent on 5, 10 and 15 mg versus minus 3.1 on placebo; in SURMOUNT-2 (type 2 diabetes), minus 12.8 and 14.7 versus minus 3.2. These are group averages with lifestyle support; individual results varied widely.
What happens when you stop taking Mounjaro?
In SURMOUNT-4, people who had lost 20.9 per cent over 36 weeks regained an average of 14.0 per cent in the 52 weeks after switching to placebo, while those continuing lost a further 5.5 per cent. The CMI says not to stop suddenly without consulting your doctor.
Who can be prescribed Mounjaro in Australia?
As of 1 October 2026: adults with insufficiently controlled type 2 diabetes; chronic weight management with a BMI of 30 or more, or 27 to under 30 with a weight-related condition; moderate to severe sleep apnoea with obesity; and, per the current PI, type 2 diabetes from age 10 at 50 kg or more. Suitability is the doctor's decision.
Is Mounjaro on the PBS?
No. As of 1 October 2026 Mounjaro is not PBS-listed for any indication. The PBAC recommended a type 2 diabetes listing in March 2026, but the sponsor declined to proceed in April 2026. See Wegovy and the PBS for semaglutide.
Do you still need to diet and exercise on Mounjaro?
Yes, by the terms of its registration: every Australian indication is an adjunct to diet and exercise or to a reduced-calorie diet and increased physical activity. The PI also warns of malnutrition and says balanced nutritional support should be considered.
Primary sources checked for this page.
- TGA ARTG entry 439692: current Mounjaro PI (vA13.0, September 2026), sections 4.1, 4.4 and 5.1.
- TGA: registration decision, chronic weight management, 9 September 2024.
- Rosenstock et al., SURPASS-1, Lancet 2021.
- Frias et al., SURPASS-2, NEJM 2021.
- Jastreboff et al., SURMOUNT-1, NEJM 2022.
- Garvey et al., SURMOUNT-2, Lancet 2023.
- Malhotra et al., SURMOUNT-OSA, NEJM 2024.
- Aronne et al., SURMOUNT-4, JAMA 2024.
- PBS: tirzepatide medicine status.
Editorial method: primary Australian regulatory sources (TGA-approved PI, TGA registration decisions, PBS records) were checked first, peer-reviewed trial publications second. Clinical review by a named Australian health professional is pending. See the Preptide editorial policy.
Important: General information only, not medical advice. Mounjaro is a registered trademark of Eli Lilly; Preptide is independent and is not affiliated with, endorsed by or sponsored by Eli Lilly. Preptide is food, not medication, and does not prescribe, sell, recommend or promote prescription medicines. Talk to your doctor or pharmacist about any medicine. In an emergency call 000. Read our editorial policy and Health Acknowledgement.