What happens if I stop taking it?

The weight comes back, and this has been measured on purpose rather than guessed at. In SURMOUNT-4, 670 adults spent 36 weeks on the drug and lost 20.9% of their body weight. Half were then switched to a dummy injection. Over the next 52 weeks they put 14.0% back on, while the half kept on the drug lost a further 5.5%. By the end, 89.5% of those still taking it had kept at least four fifths of their loss, against 16.6% of those taken off. The protection against diabetes also fades: in the three-year trial, 17 weeks with nobody taking anything moved the diabetes rate from 1.3% to 2.4%, while the dummy group barely moved.

Does it make you lose muscle?

Some, yes. In the 124 people in SURMOUNT-1 who had body scans, about three quarters of the weight lost over 72 weeks was fat and about one quarter was lean tissue — 5.6 kg of it, a tenth of what they started with. A scan study in 190 people with type 2 diabetes found muscle volume down about 5% to 7% over 52 weeks, alongside less fat sitting inside the muscle. Whether that matters is a separate question nobody has answered. No trial in this record made grip strength, walking speed or falls a main outcome, so the scans say how much lean tissue went and nothing about what the people could still do.

Is it better than semaglutide?

For weight and for blood sugar, on the two trials that put them side by side, yes. SURMOUNT-5 gave 751 adults with obesity one drug or the other at the highest amount each could tolerate for 72 weeks: weight fell 20.2% on tirzepatide against 13.7% on semaglutide, and waist measurement 18.4 cm against 13.0 cm. SURPASS-2 gave 1,879 adults with type 2 diabetes tirzepatide or semaglutide 1 mg for 40 weeks: the long-term blood sugar reading fell 0.15 to 0.45 percentage points further and weight 1.9 to 5.5 kg further. Both trials were funded by the company that makes tirzepatide. Neither of them compared the two drugs on heart attacks, strokes or death, so that question has not been asked.

Does it protect the heart?

It has never been tested against nothing, so the honest answer is narrower than the headlines. SURPASS-CVOT put 13,165 adults with type 2 diabetes and existing artery disease on tirzepatide or on dulaglutide, another weekly injection, for a median of four years. Heart attacks, strokes and deaths from heart causes happened to 12.2% against 13.1% — enough to show tirzepatide is not worse than dulaglutide, not enough to show it is better. Where there is a dummy-injection comparison is heart failure: in 731 adults with obesity and a stiff-walled heart, death from heart causes or worsening heart failure happened to 9.9% on tirzepatide against 15.3% on dummy injections.

Is there anything to the reports about mood and suicidal thoughts?

The European regulator's safety committee reviewed this class in 2023 and 2024 and concluded in April 2024 that the available evidence does not support a causal link between GLP-1 drugs and suicidal or self-injurious thoughts and actions. That review covered five substances — dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide — and did not include tirzepatide. On the US side, the Zepbound label carried a section on suicidal behaviour and ideation and removed it in February 2026. So: no regulator currently treats this as an established effect, and tirzepatide specifically was never the subject of the review that reached that conclusion.

Is compounded or mixed-at-home tirzepatide the same thing?

Nothing in this record's evidence base tested it. Every trial cited here used the manufactured product, at fixed amounts, injected by people who had been shown how. What the reporting data suggest is that getting the amount wrong is the dominant problem outside that setting: in the US regulator's public database, the most reported single term for tirzepatide is not a symptom but "incorrect dose administered", with 28,115 reports, ahead of nausea at 14,290. "Extra dose administered" appears 9,000 times and "accidental underdose" 4,607 times. Those counts are unverified reports and cannot be turned into rates, but the ranking is hard to read any other way.

Does it stop working after a while?

Not in the sense of the body building resistance to it, on what has been measured. Antibodies against the drug appear in 51% of people, 2,570 out of 5,025 across seven adult trials, and the label does not report those antibodies making it work less well. Antibodies that actually block its action were found in 2% of the people who had antibodies at all. What does happen is that the weight curve flattens. In SURMOUNT-1 the highest amount reached 20.9% below starting weight at 72 weeks and stood at 19.7% at 176 weeks — a plateau rather than a decline in effect.

Metabolic

Tirzepatide

Also known as Mounjaro · Zepbound · LY3298176

Approved medicine

21 of 51 peptides sit at this level

Category: Metabolic
Doping status: Not banned in sport
Sources: 22
Trials: 2 trials · 3,290 people

Tirzepatide is a made-in-a-lab peptide that copies two gut hormones at once — GLP-1 and GIP — which the body normally releases after a meal to say that food has arrived. Switching both on together turns down hunger, slows the stomach and makes the pancreas release insulin when blood sugar is high. It has been an approved prescription medicine in the EU since September 2022, sold as Mounjaro, for type 2 diabetes and for weight management, and the trials behind it are large and mostly compared against a dummy injection. In the biggest of them, 2,539 adults over 72 weeks, the highest amount produced a 20.9% fall in body weight against 3.1% on the dummy. It is also one of the few compounds in this register where the evidence is good enough to say what happens when people stop: in a trial that deliberately withdrew it, weight went back up 14.0% over the following year, while the group kept on it lost a further 5.5%.

TirzepatideTrials

Trials
What it is
Sold and legal
In your body
What changed
What can go wrong
Amounts studied
What people say
Unknowns
Questions
Sources

Weight-loss trials

2 trials · 2022–2025

SURMOUNT-1 · 2022 · NEJM
Treatment-15 % … -20.9 %
placebo-3.1 %
N
2 539
WEEKS
72
The range is three separate dose arms, not an uncertainty interval.
[source] — SURMOUNT-1, NEJM 2022
SURMOUNT-5 · 2025 · NEJM
Treatment-20.2 %
semaglutide-13.7 %
N
751
WEEKS
72
The comparator is semaglutide, not placebo — hence the small gap.
[source] — SURMOUNT-5, NEJM 2025

What it is

A synthetic peptide with a fatty acid attached that switches on two receptors at once: GIP and GLP-1. In the EU it is sold as Mounjaro; the US brand name Zepbound is not on the EU market.

How it is sold, and whether it is legal

Sold as: Injection under the skin.
Legal status in the EU: Mounjaro (Eli Lilly Nederland B.V.) was approved by the European regulator on 15 September 2022 and is approved both for type 2 diabetes and for weight management. Prescription only. Tirzepatide does not appear on the 2026 WADA prohibited list. According to the trade journal EMJ Reviews it has been on WADA's monitoring programme since 1 January 2026, which is not the same thing as a ban.

What it does in your body

6 parts of the body · all measured in people

Unlike pure GLP-1 analogues, tirzepatide acts on both the GLP-1 receptor and the receptor for GIP, another gut hormone. The result is more insulin release and less appetite; the fatty acid chain makes it stick to a blood protein so it lasts a week. The sequence is left empty because the molecule contains two building blocks outside the standard set that cannot be written in one-letter code.

Appetite and hunger: Hunger falls, and this is the effect people notice first. In the diabetes trials it showed up as a reported side effect — people said their appetite had gone — and it rose with the amount given. Nobody in these trials measured hunger directly; what was measured was what people ate, what they weighed, and how many of them said their appetite had dropped. The effect lasts only while the drug does: in the three-year trial, a 17-week gap with nobody taking anything was enough for the protection against diabetes to start slipping, and in the withdrawal trial weight climbed back.; Measured indirectly, through what people ate and weighed, in 2,539 adults with obesity over 72 weeks and again at 176 weeks; reduced appetite was also recorded as a side effect in the diabetes trials, in 5% at 5 mg, 10% at 10 mg and 11% at 15 mg against 1% on the dummy injection in 953 adults.; Measured in people; Source [01]Source [08]Source [09]
Stomach and gut: The stomach empties more slowly. That is part of how the drug makes a meal feel bigger, and it is also why more than half of the people in the weight trials had some gut trouble. Feeling sick is the most common single complaint, followed by loose stools, being sick and constipation. It clusters in the first few months, while the amount being given is going up, and it settles for most people. In a minority it does not: severe gut reactions were recorded in 1.7% to 3.1% of people on tirzepatide, against 1% on the dummy injection.; Counted in the pooled weight trials behind the US label: 958 adults on dummy injections against 630, 948 and 941 on the three amounts. European labelling puts any gut side effect at 55.6% to 55.8% on tirzepatide against 29.7% on dummy injections in the weight trials, and at 37.1% to 43.6% against 20.4% in the diabetes trials.; Measured in people; Source [10]Source [11]
Muscle, as well as fat: Weight does not come off as fat alone. When a group of people in the biggest weight trial had body scans, roughly three quarters of what they lost was fat and roughly one quarter was lean tissue — muscle, organs and the water they hold. In absolute terms that was 5.6 kg of lean tissue, a fall of about a tenth. A separate scan study in people with type 2 diabetes found muscle volume down by about 5% to 7%, and at the same time found less fat sitting inside the muscle than before.; Measured by body scan in 124 adults in the tirzepatide groups of SURMOUNT-1 over 72 weeks, who lost 21.3% of body weight on average, and by MRI in 190 adults with type 2 diabetes over 52 weeks, where the comparison was a long-acting insulin rather than a dummy injection.; Measured in people; Source [12]Source [13]
Blood sugar and the pancreas: Tirzepatide makes the pancreas release insulin when blood sugar is high and holds back glucagon, the hormone that pushes sugar up. Because the insulin release depends on the sugar being high in the first place, the drug on its own rarely drops blood sugar too low. Combined with the older diabetes medicines that force insulin out regardless, it does: low blood sugar was recorded in 10.3% of people also taking a sulfonylurea against 2.1% of those not. In people who did not have diabetes yet, it largely stopped them getting it.; Blood sugar measured in 1,879 adults with type 2 diabetes over 40 weeks, where the long-term sugar reading fell by 2.01 to 2.30 percentage points; progression to diabetes measured in 1,032 adults with obesity and pre-diabetes over 176 weeks; low blood sugar rates counted in the trials behind the US labels.; Measured in people; Source [02]Source [08]Source [10]
Heart and blood vessels: The resting heart beats faster on tirzepatide. A jump of 15 beats a minute or more was recorded in 10% of people on the highest amount, against 4.3% on dummy injections. Against that, in people who already had heart disease it did not increase heart attacks or strokes compared with another injected diabetes drug. In people with a stiff-walled kind of heart failure it cut the number who died of heart causes or got worse. The biggest weight trial also reported improvements in every heart-and-metabolism measure it had planned to look at.; Heart attacks, strokes and cardiovascular deaths counted in 13,165 adults with type 2 diabetes and existing artery disease over a median of four years, against dulaglutide rather than against nothing. Heart failure outcomes measured in 731 adults with obesity and heart failure with a preserved pumping fraction, followed for a median of 104 weeks. Heart rate measured in the trials behind the US label; the heart-and-metabolism measures in 2,539 adults over 72 weeks.; Measured in people; Source [01]Source [09]Source [14]Source [15]
Liver, gallbladder and kidneys: Fat inside the liver falls sharply — further than it did in the people randomly assigned to a long-acting insulin instead. The gallbladder goes the other way: stones and inflammation of the gallbladder are more common on the drug than off it. That is what usually happens when anyone loses weight quickly, by any method. The kidneys are a mixed picture. Severe vomiting and diarrhoea can dry a person out badly enough to injure the kidneys, and cases have been reported since the drug went on sale. But over four years, fewer people on tirzepatide had serious kidney trouble than on the drug it was compared against.; Liver fat measured by MRI in 296 adults with type 2 diabetes over 52 weeks. Gallbladder events counted in the pooled weight trials behind the US label, at 1.1% against 1% for stones and 0.7% against 0.2% for an inflamed gallbladder. Kidney outcomes counted in 13,165 adults over a median of four years, against dulaglutide.; Measured in people; Source [10]Source [11]Source [13]Source [16]

What changed when it was measured

13 findings · all measured in people

SURMOUNT-1 (NEJM 2022, 2,539 participants, 72 weeks) gave between −15.0% and −20.9% weight change across the three dose groups against −3.1% for placebo. SURPASS-2 (NEJM 2021, 1,879 participants, 40 weeks) compared it directly against semaglutide and gave a 0.15–0.45 percentage point greater drop in HbA1c and 1.9–5.5 kg more weight loss. SURMOUNT-5 (NEJM 2025, 751 participants, 72 weeks) gave −20.2% against −13.7% for semaglutide.

Slow to build, slow to leave, and the weight curve runs on a much longer clock than the side effects. The drug takes about five days to halve in the blood, and reaches a steady level after roughly four weeks of weekly injections. Gut symptoms arrive early and cluster in the first 20 weeks, while the amount is being stepped up, and settle for most people after that. Weight comes off steadily for well over a year: SURMOUNT-1 was still measuring falls at 72 weeks, and in SURMOUNT-4 the people kept on the drug lost a further 5.5% between week 36 and week 88. By three years the curve has flattened, with the highest amount at 19.7% below starting weight against 20.9% at 72 weeks. The sleep apnoea trials measured breathing at week 20 and week 52 only, so nothing is known about what happens before week 20. Stopping reverses it: 52 weeks after switching to dummy injections, people had put 14.0% back on.

Body weight in adults with obesity and no diabetes: Weight fell 15.0% on the 5 mg amount, 19.5% on 10 mg and 20.9% on 15 mg, against 3.1% on a dummy injection. On the highest amount, 57% of people lost at least a fifth of their body weight, against 3% on the dummy.; 2,539 adults with obesity and no type 2 diabetes, 72 weeks; Measured in people; Source [01]
Weight regained after the drug was deliberately taken away: Everyone spent 36 weeks on the drug first and lost 20.9% on average. Over the next 52 weeks the people kept on it lost a further 5.5%, while the people switched to a dummy injection put 14.0% back on — a gap of 19.4 percentage points. By the end, 89.5% of those still on the drug had kept at least four fifths of what they had lost, against 16.6% of those taken off it.; 670 adults with obesity who completed a 36-week lead-in and were then randomised to continue or to switch to dummy injections, 52 further weeks; Measured in people; Source [17]
Getting type 2 diabetes, in people who had pre-diabetes to start with: 1.3% of the people on tirzepatide were diagnosed with type 2 diabetes over three years, against 13.3% on dummy injections. After a further 17 weeks with nobody taking anything, the figures were 2.4% and 13.7%.; 1,032 adults with obesity and pre-diabetes inside a 2,539-person trial, 176 weeks plus a 17-week gap with no drug; Measured in people; Source [08]
Body weight over three years rather than eighteen months: Weight was down 12.3% on 5 mg, 18.7% on 10 mg and 19.7% on 15 mg at 176 weeks, against 1.3% on dummy injections. The 15 mg figure is slightly below where the same trial stood at 72 weeks, so the curve flattens rather than continuing down.; 2,539 adults with obesity, 176 weeks; Measured in people; Source [08]
Weight, head to head against semaglutide: Weight fell 20.2% on tirzepatide against 13.7% on semaglutide. Waist measurement fell 18.4 cm against 13.0 cm. Both drugs were pushed to the highest amount each person could tolerate.; 751 adults with obesity and no type 2 diabetes, randomised to one drug or the other, 72 weeks; Measured in people; Source [03]
Long-term blood sugar reading, head to head against semaglutide: The three-month average blood sugar reading fell by 2.01, 2.24 and 2.30 percentage points on the three amounts of tirzepatide, against 1.86 on semaglutide 1 mg — differences of 0.15, 0.39 and 0.45 points. Weight fell 1.9, 3.6 and 5.5 kg further than on semaglutide.; 1,879 adults with type 2 diabetes already taking metformin, 40 weeks; Measured in people; Source [02]
Body weight in people who have type 2 diabetes as well as obesity: Weight fell 12.8% on 10 mg and 14.7% on 15 mg, against 3.2% on dummy injections. Between 79% and 83% lost at least a twentieth of their body weight, against 32% on the dummy. The figures are smaller than in people without diabetes, which is the usual pattern for this class.; 938 adults with obesity and type 2 diabetes, 72 weeks; Measured in people; Source [18]
Breathing stoppages during sleep: In people not using a sleep mask, the number of times breathing stopped or went shallow per hour fell by 25.3 against 5.3 on dummy injections. In people who were using a mask, it fell by 29.3 against 5.5. Weight fell 17.7% and 19.6% against 1.6% and 2.3%. Enough people improved that 42.2% and 50.2% reached a level counted as remission or mild disease without daytime sleepiness, against 15.9% and 14.3%.; 469 adults with moderate to severe obstructive sleep apnoea and obesity across two trials, 234 and 235 people, 52 weeks each; Measured in people; Source [19]Source [20]
Heart attacks, strokes and death from heart causes: 12.2% of people on tirzepatide had one of these against 13.1% on dulaglutide, another weekly injected diabetes drug. Trials put that gap as a hazard ratio — the risk on one drug divided by the risk on the other, where 1 means no difference. Here it was 0.92, with a range running from 0.83 to 1.01. Because that range still touches 1, the trial showed tirzepatide is not worse than dulaglutide but could not show it is better. There was no dummy-injection group, so this trial cannot say what tirzepatide does against no drug at all.; 13,165 adults with type 2 diabetes and existing artery disease, median four years; Measured in people; Source [14]
Heart failure getting worse, in people with a stiff-walled heart: Death from heart causes or a worsening of heart failure happened to 9.9% on tirzepatide against 15.3% on dummy injections — a hazard ratio of 0.62. Almost all of that came from fewer heart-failure events, 8.0% against 14.2%. Deaths from heart causes were 2.2% against 1.4%, a difference too small and too uncertain to read either way. Symptom and quality-of-life scores improved 19.5 points against 12.7.; 731 adults with obesity and heart failure with a preserved pumping fraction, median 104 weeks of follow-up; Measured in people; Source [15]
Serious kidney events: A combined measure of protein leaking into the urine, a large drop in filtering capacity, kidney failure or death from kidney disease happened to 6.0% on tirzepatide against 7.6% on dulaglutide. The kidneys' filtering rate also fell more slowly on tirzepatide, by a small margin the paper reports as 0.29 units a year.; 13,165 adults with type 2 diabetes and existing artery disease, median four years, against dulaglutide; Measured in people; Source [16]
Fat inside the liver: Liver fat fell by 8.09 percentage points on the two higher amounts of tirzepatide against 3.38 on a long-acting insulin — a difference of 4.71 points. The size of the fall tracked how much fat came off around the organs and under the skin.; 296 adults with type 2 diabetes and a high fatty-liver score, randomised four ways, 52 weeks; Measured in people; Source [13]
How much of the lost weight was muscle rather than fat: In the people who had body scans, about three quarters of the weight lost was fat and about one quarter was lean tissue. In numbers, lean tissue fell by 5.6 kg, which was 10.9% of what they started with, while total body weight fell 21.3%. The figures are reported for the people on the drug, without a dummy-injection group beside them. The review that collected them reads the same numbers as lean mass being held in proportion rather than as a loss; the numbers themselves are the same either way.; 124 adults in the tirzepatide groups of SURMOUNT-1 who had body scans, 72 weeks; Measured in people; Source [12]

What can go wrong

17 effects, 6 serious

Stomach and bowel problems are the most common side effects and affect more than 1 in 10. In SURPASS-2, nausea was reported by 17–22%, diarrhoea by 13–16% and vomiting by 6–10%. Stopping because of side effects ran at 4.3–7.1% against 2.6% for placebo in SURMOUNT-1; there is no data on treatment lasting more than a few years.

Inflammation of the pancreasSerious: Severe pain high in the belly, often boring through to the back, usually with vomiting. The European labelling states that cases have included the destructive form, with fatal outcomes. It is rare, but it is the reason the labels tell doctors to stop the drug if pancreatitis is suspected and never to restart it if it is confirmed.; 0.2% on tirzepatide against 0.2% on dummy injections in the weight trials. In the diabetes programme, 14 confirmed events in 13 people, which works out at 0.23 people per 100 years of treatment, against 3 events in 3 people on the comparison drugs. Listed as uncommon in European labelling.; Source [09]Source [11]
Gallstones and an inflamed gallbladderSerious: Pain under the right ribs, often after a fatty meal, sometimes with fever. Some people need the gallbladder removed. Losing weight quickly causes gallstones whatever the method, so part of this is the weight loss rather than the drug, and the trials cannot separate the two.; In the pooled US weight trials, gallstones in 1.1% on tirzepatide against 1% on dummy injections, and an inflamed gallbladder in 0.7% against 0.2%. European labelling lists both as uncommon — fewer than 1 in 100.; Source [10]Source [11]
Gut symptoms bad enough to dry someone out and injure the kidneysSerious: Vomiting and diarrhoea that go on long enough to leave a person short of fluid. The US label records reports of kidney injury sent in after the drug went on sale, some of them severe enough to need dialysis. The European labelling states that these gut reactions can dry a person out and that this can worsen kidney function, including outright kidney failure.; Severe gut reactions in 1.7%, 2.5% and 3.1% of people on the three amounts in the weight trials against 1% on dummy injections. Kidney injury has been reported since the drug went on sale, without a rate.; Source [10]Source [11]
Severe allergic reactionSerious: Rash, itching and flushing at the mild end; swelling of the lips, tongue or throat and a sudden drop in blood pressure at the severe end. A known serious allergy to tirzepatide is one of the few things that bars its use outright.; Severe reactions in 0.1% on tirzepatide against 0% on dummy injections in the weight trials; hypersensitivity of any kind in 5% against 3%. The whole-body reaction that drops blood pressure, and swelling of the face and throat, are both listed as rare in European labelling — fewer than 1 in 1,000.; Source [10]Source [11]
Thyroid tumours — in rats, not so far in peopleSerious: Rats developed tumours of a particular thyroid cell. There were more of them the higher the amount and the longer the treatment. Whether the same thing happens in humans is not known. The US labels bar the drug outright for anyone with a personal or family history of medullary thyroid cancer, or of the inherited syndrome that goes with it. European labelling does not carry that bar. Calcitonin is a substance in the blood that can rise with that cancer, and a raised reading is listed in European labelling as uncommon on the diabetes side and rare on the weight-management side. The US label states that routinely checking it is of uncertain value.; Not measured in people. The US labels carry this in a boxed warning at the top, based on rats given the drug for a long time at amounts comparable to human ones.; Source [10]Source [11]
Breathing stomach contents into the lungs during an operationSerious: Because the stomach empties more slowly, food can still be sitting there when someone is put under general anaesthetic or deeply sedated, and it can go into the lungs. The labels raise it as a risk for anaesthetists to plan around.; Reported since the drug went on sale, without a rate. Listed in European labelling as a warning rather than as a counted side effect.; Source [10]Source [11]
Blood sugar dropping too low: Shakiness, sweating, confusion and, at the severe end, needing someone else's help. Tirzepatide on its own only pushes insulin out when blood sugar is already high, so it rarely does this alone. The risk comes from combining it with the older tablets and with insulin, which lower blood sugar regardless.; In the weight trial run in people who also had type 2 diabetes, 10.3% of those taking a sulfonylurea alongside it, against 2.1% of those not. Added to a long-acting insulin, a blood sugar reading below 54 mg/dL — the level labs treat as clearly low — in 14% to 19% against 13% on dummy injections. On its own in the diabetes trials, 0% to 1%.; Source [09]Source [10]
Feeling sick: The single most common complaint, and the one that most often decides whether someone stays on the drug. It clusters in the first 20 weeks while the amount is being increased, and for most people it fades. It is worse at the higher amounts.; 25%, 29% and 28% on the three amounts in the weight trials against 8% on dummy injections; 12%, 15% and 18% in the diabetes trials against 4%. Very common in European labelling — more than 1 in 10.; Source [09]Source [10]
Diarrhoea: Loose stools, often with cramping and urgency, mostly in the first months. It is the side effect most likely to leave someone short of fluid, which is the route to the kidney problems above.; 19%, 21% and 23% in the weight trials against 8% on dummy injections; 12%, 13% and 17% in the diabetes trials against 9%. Very common in European labelling.; Source [10]
Being sick: Usually arrives with the nausea and in the same window, while the amount is going up. It gets steadily more common at higher amounts, which is the clearest dose relationship in the whole side-effect table.; 8%, 11% and 13% in the weight trials against 2% on dummy injections; 5%, 5% and 9% in the diabetes trials against 2%. Very common in European labelling.; Source [10]
Constipation: Goes the opposite way to the other gut effects: it was most common on the lowest amount in the weight trials. Eating much less, which is the point of the drug, contributes to it.; 17%, 14% and 11% in the weight trials against 5% on dummy injections; 6%, 6% and 7% in the diabetes trials against 1%. Listed as common in European labelling.; Source [10]
Hair falling out: Thinning rather than bald patches, and far more often reported by women than men. The European labelling states the events were mainly mild and that most people recovered while still taking the drug. Rapid weight loss by any method causes hair shedding, so this is not necessarily the drug itself.; 4.9% on tirzepatide against 1.0% on dummy injections across three pooled weight trials in European labelling. The US label splits it by sex: 7.1% of women on the drug against 1.3% of women on dummy injections, and 0.5% of men against none.; Source [10]Source [11]
A faster resting heart: Usually noticed on a monitor rather than felt. It rises with the amount given. Listed in European labelling as a common finding, without a warning attached.; A rise of 15 beats a minute or more was recorded in 4.6%, 5.9% and 10% of people on the three amounts in the diabetes trials, against 4.3% on dummy injections.; Source [09]Source [11]
Redness, itching or pain where the needle goes in: A patch of redness, sometimes itchy, usually settling within a few days. It also dominates the reports sent to the US regulator after the drug went on sale. Injection-site pain, bleeding, redness, bruising and itching are five of the twenty-five most reported terms there.; 6%, 8% and 8% in the weight trials against 2% on dummy injections; 3.2% against 0.4% in the diabetes trials. Listed as common in European labelling.; Source [10]Source [21]
Tiredness: Reported through the trials and one of the top twenty terms in the reports sent to the US regulator. Eating substantially less will do this on its own, so the trials cannot separate the drug from the diet it produces.; 5%, 6% and 7% in the weight trials against 3% on dummy injections. Very common in European labelling.; Source [10]
Raised pancreas enzymes on a blood test: Two enzymes the pancreas makes, which rise on a blood test without the person feeling anything. The European labelling states that in the absence of symptoms of pancreatitis these rises have no established meaning. It is a common reason for alarm when someone has routine blood tests done while taking the drug.; In the diabetes trials, average rises from the starting level of 33% to 38% in amylase and 31% to 42% in lipase. In the weight trials, 23% to 28% in amylase and 32% to 39% in lipase.; Source [11]
Antibodies against the drug: The immune system learns to recognise the molecule and makes antibodies against it. In most people this has no visible consequence, and the label does not report the drug working less well. Some of those antibodies also latch on to the body's own versions of the two hormones: 34% of them for one hormone and 14% for the other. What that does over years is not established.; 51% of people, 2,570 out of 5,025 across seven adult trials, developed antibodies to tirzepatide. Among children in a 30-week trial, 30 out of 61. Antibodies that block the drug's action were found in 2% of those who had antibodies at all.; Source [09]

Who it is known to be dangerous for

The European labelling bars it outright for one group only: people with a known allergy to tirzepatide or to anything else in the injection. The US labels add a second outright bar. Anyone with a personal or family history of medullary thyroid cancer, or of the inherited syndrome called MEN 2, is excluded there, because of the thyroid tumours seen in rats. Beyond those two bars, both labels name groups where harm is documented. Pregnancy is the clearest: the European labelling states that tirzepatide should not be used during pregnancy, animal studies showed harm to the developing young, and there is no human trial. Anyone relying on the contraceptive pill is another, because the slowed stomach can stop the pill being absorbed properly. Three more groups are named for caution. Anyone who has had inflammation of the pancreas before. Anyone whose stomach already empties too slowly, the condition called gastroparesis. And anyone with diabetic eye disease that is active or being treated, where both labels urge caution and neither can point to a trial. Anyone on insulin, or on the older sulfonylurea tablets, is at several times the risk of blood sugar dropping too low. And anyone being put under general anaesthetic is at risk of breathing stomach contents into the lungs, which is why the anaesthetist needs to know.

The amounts the studies used

9 amounts

These are the amounts the studies below gave their participants, and they are here as facts about those studies. They are not a recommendation, not a starting point and not a range to pick from. What a person should take, if anything, is a question for a doctor who knows them.

SURMOUNT-1, weight in 2,539 adults with obesity and no diabetes: 5 mg, 10 mg or 15 mg once a week, injected under the skin, as three separate fixed groups; 72 weeks, extended to 176 weeks in the same trial; Source [01]Source [08]
SURMOUNT-2, weight in 938 adults who had type 2 diabetes as well as obesity: 10 mg or 15 mg once a week, injected under the skin; 72 weeks; Source [18]
SURMOUNT-4, the withdrawal trial: 670 adults were kept on the drug or switched to dummy injections: The highest amount each person could tolerate, 10 mg or 15 mg once a week, injected under the skin; 36 weeks on the drug for everyone, then 52 further weeks; Source [17]
SURMOUNT-5, head to head against semaglutide in 751 adults with obesity: The highest amount each person could tolerate, 10 mg or 15 mg of tirzepatide once a week, against 1.7 mg or 2.4 mg of semaglutide once a week; 72 weeks; Source [03]
SURPASS-2, blood sugar in 1,879 adults with type 2 diabetes on metformin: 5 mg, 10 mg or 15 mg once a week, against semaglutide 1 mg once a week; 40 weeks; Source [02]
SURPASS-CVOT, heart outcomes in 13,165 adults with type 2 diabetes and existing artery disease: Up to 15 mg once a week, against dulaglutide 1.5 mg once a week; Median four years; Source [14]
SURMOUNT-OSA, sleep apnoea in 469 adults across two trials: The highest amount each person could tolerate, 10 mg or 15 mg once a week; 52 weeks; Source [19]
SUMMIT, heart failure with a preserved pumping fraction in 731 adults with obesity: Up to 15 mg once a week, injected under the skin; At least 52 weeks of treatment, median 104 weeks of follow-up; Source [15]
SURPASS-3 MRI sub-study, liver and abdominal fat in 296 adults with type 2 diabetes: 5 mg, 10 mg or 15 mg once a week, against a daily long-acting insulin; 52 weeks; Source [13]

What people report

What follows is what people say online. It is not evidence, it is not graded, and it is not checked by anyone. People who had a bad time and people who are selling something both post more than people for whom nothing happened. It is here because you would go and read it anyway, and knowing who is talking is better than not.

The constant thinking about food stops

Across three published interview studies, the change people name first is not hunger but the mental noise around food. Thirty people interviewed for a 2026 study described a fall in what they called food noise, psychological hunger or appetite. In a separate study of eight women, one said that not having the food noise had drastically increased her quality of life, even if she never lost another pound. In a Japanese study of 29 people who had been in a trial, 75.9% described losing their appetite while on the drug and 72.4% said they had deliberately changed how they ate.

Read in Three published interview studies — 30 adults in the United States recruited through the ResearchMatch registry, 8 women in the Washington DC area, and 29 Japanese participants interviewed after leaving the SURMOUNT-J trial