Does this mean liraglutide causes pancreatic cancer?

No. A pancreatic carcinoma PRR of 18.6 in a spontaneous reporting database means reports pairing the two appear far more often than the background pattern predicts. Where an association has been discussed in the literature for over a decade, clinicians who see the event are more likely to attribute it to the drug and report it, which produces exactly this pattern in the absence of any causal effect. Cohort studies with denominators are what settle the question.

Why does tirzepatide look safest here?

Partly because its signals are genuinely weaker in this data, and partly because it is the newest of the three. Time on market drives reporting independently of risk, so a comparison across drugs of different vintages is systematically biased in favour of the newer one.

Are these drugs kidney-protective or kidney-harmful?

Randomised outcome trials in this class have shown kidney benefits in defined populations, and spontaneous reports have raised acute kidney injury as a signal. Both can be true: a chronic benefit and an acute risk in particular circumstances - dehydration from vomiting or diarrhoea being the obvious mechanism - are not contradictory.

Should any of this change what someone takes?

That is a conversation for a prescribing clinician, not a reference article. These are licensed medicines; nothing supplied on this site is an alternative to any of them, and no article here should be used to inform a decision about a prescription.

Research & Regulatory News

Which Drug Signals Where, and What That Is Worth

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-233 cited sources

Shokr and colleagues analysed FAERS reports for three weight-management agents across gastrointestinal, renal and pancreatic outcomes. Semaglutide showed the strongest gastrointestinal signals, liraglutide showed the strongest renal and pancreatic ones, and tirzepatide showed weaker or absent signals across most of the outcomes examined.

Key facts

Publication: Pharmaceuticals (Basel) 2026;19(1):136 (PMID 41599734)
Method: Disproportionality analysis of FAERS, PRR and ROR with 95% CIs
Window: From each drug's approval for weight management
Strongest GI signal: Semaglutide, PRR 3.97, ROR 14.21 (n=12,321)
Liraglutide GI: PRR 2.76, ROR 5.01 (n=5,972)
Tirzepatide GI: PRR 1.64, ROR 1.90 (n=4,056)
Acute pancreatitis, liraglutide: PRR 18.9, ROR 19.4
Diabetic ketoacidosis, semaglutide: PRR 5.86, ROR 5.9
Declared conflicts: None

What was compared

The analysis looked at gastrointestinal, renal and pancreatic adverse events for GLP-1 and dual receptor agonists, using FAERS data from each drug's approval for weight management, with signals identified by proportional reporting ratio and reporting odds ratio with 95% confidence intervals. The comparator is the rest of the database rather than another drug, which matters for how the numbers should be read: each figure describes how a drug-event pair stands against the overall background pattern, not against another agent in the class.

The gastrointestinal result and its internal oddity

Semaglutide showed the strongest gastrointestinal signals, with 12,321 reports representing 1.65% of its total and a PRR of 3.97 alongside an ROR of 14.21. Liraglutide followed at 5,972 reports, 0.45%, PRR 2.76, ROR 5.01. Tirzepatide was lowest on the ratios at 4,056 reports, PRR 1.64, ROR 1.90 - though its 3.48% proportion is the highest of the three, which is a useful reminder that the proportion and the disproportionality measure answer different questions. The gap between semaglutide's PRR of 3.97 and its ROR of 14.21 is unusually wide. PRR and ROR converge when the event is a small share of the drug's reports and diverge when it is a large one, so a spread that size is itself information about the composition of the reports rather than about risk.

Renal and pancreatic: liraglutide leads, which is the counterintuitive part

For renal and pancreatic outcomes the ordering inverts. Liraglutide showed the highest overall signal (PRR 4.91, ROR 5.35), driven by acute pancreatitis (PRR 18.9, ROR 19.4) and pancreatic carcinoma (PRR 18.6, ROR 19.5). Semaglutide showed stronger associations with diabetic ketoacidosis (PRR 5.86, ROR 5.9) and acute kidney injury (PRR 1.25, ROR 1.25). Tirzepatide showed weaker or absent signals across most outcomes. The liraglutide pancreatic figures are the largest in the analysis by a wide margin, and they belong to the oldest and least-used of the three agents - which is exactly the configuration in which reporting artefacts are most likely, because a drug marketed since 2010 has accumulated years of literature associating GLP-1 agonism with pancreatitis, and notoriety bias increases reporting of an association once it is expected.

Reading tirzepatide's weaker signals correctly

Tirzepatide comes out cleanest across most of this analysis, and the temptation is to read that as a safety advantage. It may be one. It is also what a drug approved in 2022 looks like relative to drugs approved in 2010 and 2017, in a system where reporting accumulates with time on market, with literature attention, and with the number of clinicians who have learned to associate a drug with an event. A signal that is absent may be absent because the association does not exist, or because not enough time has passed for it to surface. Disproportionality cannot distinguish the two.

Where this fits against the drug-versus-drug analyses

Compare this with Gandhi and colleagues, who set tirzepatide directly against semaglutide for acute kidney injury and found a reporting odds ratio of 0.44 (95% CI 0.38 to 0.50). Both analyses agree that semaglutide's kidney-injury reporting exceeds tirzepatide's. They differ enormously in magnitude - 1.25 against the whole database, 0.44 in the reciprocal direction against semaglutide specifically - because they are measuring against different reference groups. Neither is wrong and neither is a risk estimate.

What the authors themselves conclude

The paper's own conclusion is appropriately narrow: that semaglutide was most associated with gastrointestinal events and liraglutide with renal and pancreatic signals, that novel associations with ketoacidosis and acute kidney injury warrant clinical vigilance, and that the findings should be cautiously interpreted given surveillance limitations, with large-scale real-world studies needed to confirm safety profiles. The authors declare no conflicts of interest. That framing - a signal is a prompt for a properly designed study, not a result - is the one that should survive into any summary of this work, and it is usually the first thing to be dropped.

Extended research context

The Research & Regulatory News deep dive

Deep dive: why 2026 was the year the incretin field split in two

For a decade every meaningful GLP-1 medicine was a peptide, and every one of them was injected. 2026 broke that pattern in both directions at once. In August the MHRA authorised orforglipron, a small molecule with no peptide bonds that works as an ordinary daily tablet. Three months earlier, retatrutide's TRIUMPH-1 reported a 28.3% mean weight reduction — the largest figure yet from a single molecule, and achievable only with a peptide capable of engaging three receptors at once. The field is not converging on one answer; it is separating into a convenience track and a magnitude track, and those tracks have different chemistry.

Deep dive: what a marketing authorisation actually means

An authorisation is granted to a specific product, in a specific formulation, for a specific indication, by a specific regulator. It is not a statement about a compound class and it does not transfer. Orforglipron being licensed in the UK tells you nothing about the legal or regulatory status of any other incretin, and nothing at all about compounds that remain investigational. Authorisation is also separate from funding: a licensed medicine is not automatically available on the NHS, which requires a further NICE appraisal.

Deep dive: reading trial results without being misled

Headline percentages are the least transferable part of a trial. A figure is only meaningful alongside its population, its duration, its comparator and its dropout rate. TRIUMPH-1's 28.3% came from an 80-week study in a relatively uncomplicated obesity population; TRIUMPH-3's 22.6% came from adults with severe obesity and established cardiovascular disease, and the gap between those two numbers is mostly population, not potency. Discontinuation rates deserve the same attention as efficacy: 11.3% of the TRIUMPH-1 12 mg arm stopped due to adverse events against 4.9% on placebo, and that figure is routinely dropped from summaries.

Research applications

▸Tracking regulatory status of investigational incretin compounds
▸Understanding the difference between authorisation, NICE appraisal and NHS availability
▸Comparing peptide and non-peptide receptor agonist pharmacology
▸Interpreting Phase 3 topline releases before peer-reviewed publication
▸Verifying trial identity against ClinicalTrials.gov registrations

Handling checklist

✓Check the compound named in a trial registration matches the compound being discussed
✓Confirm the NCT identifier resolves to the acronym being cited
✓Read topline press releases as preliminary until peer-reviewed publication
✓Separate the trial population from the headline percentage before comparing studies
✓Treat authorisation in one jurisdiction as saying nothing about status in another

Common research-handling mistakes

Learnt from thousands of researcher orders across our UK labs.

✗ Treating a positive Phase 3 as approval

Fix: Filing begins a review that commonly takes a year or more and can end in a request for more data.

✗ Comparing weight-reduction percentages across different trials

Fix: Population, duration and comparator differ; the numbers are not interchangeable.

✗ Assuming one incretin's approval legitimises another compound

Fix: Authorisations are product-specific and do not transfer between compounds.

✗ Citing a TRIUMPH number without checking the NCT identifier

Fix: Verify against ClinicalTrials.gov — the numbering has been widely misreported.

✗ Reading research material as an alternative to a licensed medicine

Fix: Research material is supplied for laboratory use only and is not a substitute for anything prescribed.

Continue researching

Peer-reviewed guides, comparators and matched reference materials.

Frequently asked questions

Does this mean liraglutide causes pancreatic cancer?: No. A pancreatic carcinoma PRR of 18.6 in a spontaneous reporting database means reports pairing the two appear far more often than the background pattern predicts. Where an association has been discussed in the literature for over a decade, clinicians who see the event are more likely to attribute it to the drug and report it, which produces exactly this pattern in the absence of any causal effect. Cohort studies with denominators are what settle the question.
Why does tirzepatide look safest here?: Partly because its signals are genuinely weaker in this data, and partly because it is the newest of the three. Time on market drives reporting independently of risk, so a comparison across drugs of different vintages is systematically biased in favour of the newer one.
Are these drugs kidney-protective or kidney-harmful?: Randomised outcome trials in this class have shown kidney benefits in defined populations, and spontaneous reports have raised acute kidney injury as a signal. Both can be true: a chronic benefit and an acute risk in particular circumstances - dehydration from vomiting or diarrhoea being the obvious mechanism - are not contradictory.
Should any of this change what someone takes?: That is a conversation for a prescribing clinician, not a reference article. These are licensed medicines; nothing supplied on this site is an alternative to any of them, and no article here should be used to inform a decision about a prescription.

Primary sources & clinical trials

Peer-reviewed research and registered trials from PubMed, ClinicalTrials.gov, PubChem, FDA and NIH. All links open in a new tab and point to the primary source, so every claim can be verified at origin.

Written and reviewed by

Jack Muncaster · Founder, UK Peptides

Jack founded UK Peptides in Manchester after repeatedly receiving research compounds with missing or recycled paperwork. He is responsible for supplier selection, batch release decisions and the content published in this research library. Every article here is sourced to primary literature and every product page to a signed third-party certificate.

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