Questions about GLP-1 long-term safety usually come down to one thing: is it safe to take these medicines for years? The evidence covers up to about four years in large trials, and semaglutide has been authorised in the UK since 2018. Over that span the serious risks are well described: some are common (gallstones), others very rare (NAION with semaglutide). Effects over decades are not yet known, and the two newest tablets have the shortest record.

This guide covers semaglutide (the Wegovy injection and pill, and Ozempic and Rybelsus for type 2 diabetes), tirzepatide (Mounjaro) and orforglipron (Foundayo). It is information only, not medical advice: all are prescription-only, and a prescriber decides whether one suits you. For everyday problems such as nausea, see managing GLP-1 side effects.

Key takeaway

The biggest safety studies have run for roughly two to four years. Known serious risks include pancreatitis (uncommon), gallstones (common) and, with semaglutide, a very rare eye condition called NAION. Evidence on decades of use, and on the newest tablets, is still being gathered, so regular reviews and Yellow Card reports matter.

GLP-1 long-term safety: how long have the trials run?

Most weight-management licensing trials lasted under two years:

  • Wegovy injection: STEP 1 to 4 ran for 68 weeks; STEP 5 followed 304 people for two years.
  • Mounjaro: SURMOUNT-1 ran for 72 weeks; a later analysis followed the 1,032 participants with prediabetes through 176 weeks and reported no new safety signals.
  • Wegovy pill: OASIS 4 ran for 64 weeks.
  • Foundayo: the ATTAIN weight trials ran for 72 weeks.

The longest evidence comes from heart-outcome trials. SELECT followed 17,604 adults on Wegovy 2.4 mg or placebo for a mean of 39.8 months; SURPASS-CVOT followed 13,299 adults with type 2 diabetes on tirzepatide or another GLP-1 medicine, dulaglutide, for a median of 4.0 years. So “long-term” still means a few years, not decades.

What the SELECT heart trial found

SELECT (New England Journal of Medicine, 2023) enrolled people aged 45 or over with established heart or circulatory disease, a BMI of 27 or more and no diabetes. A first heart attack, stroke or cardiovascular death occurred in 6.5% on semaglutide and 8.0% on placebo. Adverse events led 16.6% of the semaglutide group to stop treatment, against 8.2% on placebo. The UK SmPC records more hip and pelvis fractures on Wegovy than placebo in women and people aged 75 and over (see GLP-1 medications and muscle loss). The manufacturer funded the trial, and its result applies to people like those enrolled.

Known serious risks, and how often they occur

The UK SmPCs for Mounjaro, Wegovy (injection and tablets) and Foundayo give these warnings. Common means up to 1 in 10 people, uncommon up to 1 in 100, very rare up to 1 in 10,000.

  • Acute pancreatitis: uncommon for all four; in the Wegovy injection’s main weight trials (STEP), confirmed cases affected 0.2% on semaglutide versus under 0.1% on placebo. In January 2026 the MHRA strengthened warnings for GLP-1 medicines to highlight rare necrotising and fatal cases. It had received 1,296 UK Yellow Card reports of pancreatitis between 2007 and October 2025, 19 of them fatal; report numbers do not show how often pancreatitis happens. None of the four has been studied in people with previous pancreatitis.
  • Gallstones: common; the Mounjaro and Foundayo SmPCs link gallbladder problems to weight reduction.
  • Dehydration and the kidneys: sickness and diarrhoea can cause dehydration, which can worsen kidney function, including acute kidney failure (Mounjaro) or injury (Foundayo).
  • Low blood sugar: more likely alongside insulin or a sulfonylurea, whose dose may need lowering.
  • Diabetic eye disease: rapidly improving blood sugar has been linked to temporary worsening of diabetic retinopathy; with semaglutide, people with retinopathy who also used insulin had more complications.
  • NAION: sudden, painless vision loss from reduced blood flow to the optic nerve. In June 2025 the European Medicines Agency’s safety committee concluded it is a very rare side effect of semaglutide; studies in type 2 diabetes suggested about one extra case per 10,000 person-years. The MHRA issued matching advice in February 2026.
  • Anaesthesia and sedation: slower stomach emptying means stomach contents could be inhaled under general anaesthesia or deep sedation, so the MHRA asks you to tell your healthcare team, including the anaesthetist.

The thyroid question: findings in rodents

In two-year animal studies, semaglutide caused thyroid C-cell tumours in rats and mice, and tirzepatide in rats. The semaglutide SmPC says rodents are particularly sensitive to the mechanism, and the relevance for humans is “considered to be low, but cannot be completely excluded”. The Mounjaro SmPC calls the human relevance unknown. Orforglipron is not active in rats or mice, so its SmPC cites the class finding with the same wording. The tumours appear only in the SmPCs’ animal-study section, not among side effects in people. The Mounjaro SmPC does list raised blood calcitonin, a hormone these cells make, as common in its weight trials.

What is still being studied

  • Use over decades. No trial has run this long, and the Wegovy and Mounjaro SmPCs note limited experience in people aged 85 and over.
  • The newest tablets. The Wegovy pill and Foundayo were authorised in the UK in 2026. Mounjaro, Wegovy (injection and tablets) and Foundayo all carry a black triangle, meaning additional monitoring.
  • NAION beyond semaglutide. In February 2026 the MHRA said it was reviewing any evidence of a link with other GLP-1 medicines.
  • Genes and pancreatitis. In 2025 the MHRA and Genomics England began a Yellow Card Biobank study of whether genes affect pancreatitis risk on these medicines.

Stopping is part of the long-term picture

Benefits tend to fade when treatment ends: a year after stopping semaglutide in the STEP 1 extension, people had regained about two-thirds of the weight lost. See stopping a GLP-1 medicine.

Why monitoring and reporting matter

Trials of a few thousand people can miss very rare effects. The NAION warning rests largely on large population studies, and the stronger pancreatitis warning on reports made after licensing.

  • Keep your prescriber’s reviews; the SmPCs ask for a decision on continuing if less than 5% of body weight has been lost after six months on the Wegovy injection, or six months after reaching the highest tolerated dose of Mounjaro.
  • Tell your GP and any doctor treating you that you take a GLP-1 medicine; the MHRA warns that private prescriptions may not appear in your record.
  • Report suspected side effects to the MHRA Yellow Card scheme. Patients and carers can report, and a report does not mean the medicine was definitely the cause.

Drug-by-drug detail is on our Mounjaro, Wegovy, Wegovy pill and Foundayo pages.

Frequently asked questions

Is it safe to take a GLP-1 medicine for years?

Large trials have followed people for up to about four years. The serious risks seen so far are well described, some common (gallstones), others very rare (NAION with semaglutide), but effects over decades are unknown, so your prescriber should review treatment regularly.

Do GLP-1 medicines cause thyroid cancer?

Thyroid C-cell tumours were seen in rodents given semaglutide or tirzepatide. The UK SmPCs call the relevance to humans low but not excluded (semaglutide) or unknown (tirzepatide), and do not list thyroid tumours among side effects in people.

How rare is NAION with semaglutide?

Very rare: it may affect up to 1 in 10,000 people taking semaglutide. For sudden loss of vision or rapidly worsening eyesight, the MHRA advises going urgently to eye casualty or A&E.

Does Wegovy lower cardiovascular risk?

In SELECT, a first heart attack, stroke or cardiovascular death occurred in 6.5% of adults on semaglutide 2.4 mg and 8.0% on placebo. Everyone enrolled had established heart or circulatory disease and no diabetes, so the finding applies to people like them.

Are the GLP-1 tablets as well studied as the injections?

Not yet. Their main weight trials ran for 64 and 72 weeks, and both were authorised in the UK in 2026. The Wegovy pill shares its molecule with the longer-studied Wegovy injection.

Sources

  1. SmPCs (emc), sections 4.4, 4.8, 5.1 and 5.3: Wegovy 2.4 mg FlexTouch, Wegovy tablets, Mounjaro KwikPen, Foundayo.
  2. MHRA Drug Safety Updates: acute pancreatitis (January 2026), semaglutide and NAION (February 2026), aspiration under anaesthesia (January 2025).
  3. MHRA: Yellow Card Biobank pancreatitis study (June 2025).
  4. EMA: PRAC conclusion on NAION and semaglutide (June 2025).
  5. Lincoff AM et al., SELECT, N Engl J Med 2023 (PubMed); Jastreboff AM et al., SURMOUNT-1 176-week analysis, N Engl J Med 2025 (PubMed); Wilding JPH et al., STEP 1 extension, Diabetes Obes Metab 2022 (PubMed).

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