"Which GLP-1 has the fewest side effects?" is a fair question with an unsatisfying honest answer: nobody has run the trial that would settle it. No study has given every GLP-1 medicine to comparable people and counted the side effects. What exists is narrower and more useful than a ranking: five trials that compare pairs of drugs directly, and the labels' own figures on how many people stopped.
This page reads both, as of 26 September 2026. It does not say which medicine anyone should take — that depends on a person's health, other medicines and goals, and it is a decision for their prescriber. The side-effect record of each drug is on its own page (Wegovy, Zepbound, Ozempic, Mounjaro), and the class picture is on the GLP-1 side effects hub.
Why the labels cannot rank them
Every GLP-1 label prints an adverse-reaction table, and it is tempting to line them up. The labels themselves warn against it: rates observed in one drug's trials "cannot be directly compared" with another's. The reason is visible in the placebo column. Nausea on a dummy injection was 16% in the Wegovy weight trials and 8% in the Zepbound weight trials — the same symptom, recorded differently in two trial programmes. Some labels also build a single row from different lists of terms, which we set out for fatigue.
So the only clean comparison is a trial that randomised people to one drug or the other. There are five.
The five head-to-head trials
| Trial | Drugs compared | Who | Gastrointestinal events | Stopped for adverse events |
|---|---|---|---|---|
| SURMOUNT-5 (72 wk) | tirzepatide ≤15 mg vs semaglutide ≤2.4 mg | 751 adults with obesity | nausea 43.6% vs 44.4%; vomiting 15.0% vs 21.3% | serious AEs 4.8% vs 3.5% |
| SURPASS-2 (40 wk) | tirzepatide 5, 10, 15 mg vs semaglutide 1 mg | adults with type 2 diabetes | nausea 17–22% vs 18%; vomiting 6–10% vs 8% | serious AEs 5–7% vs 3% |
| STEP 8 (68 wk) | semaglutide 2.4 mg vs liraglutide 3 mg | 338 adults with obesity | any GI event 84.1% vs 82.7% | stopped for any reason 13.5% vs 27.6% |
| SUSTAIN 7 (40 wk) | semaglutide 0.5 / 1 mg vs dulaglutide 0.75 / 1.5 mg | 1,201 adults with type 2 diabetes | 43% / 44% vs 33% / 48% | GI the most common reason in both |
| ACHIEVE-3 (52 wk) | orforglipron 12 / 36 mg vs oral semaglutide 7 / 14 mg | 1,698 adults with type 2 diabetes | 59% / 58% vs 37% / 45% | 9% / 10% vs 4% / 5% |
SURMOUNT-5 figures are our arithmetic from the counts posted on ClinicalTrials.gov; the others are from the published abstracts. Read row by row, they say different things.
Tirzepatide against semaglutide. In SURMOUNT-5 the stomach side effects were close to a tie: nausea within one point, diarrhoea identical, vomiting lower on tirzepatide. Serious adverse events went the other way, 18 people against 13. SURPASS-2, in type 2 diabetes against the lower 1 mg semaglutide dose, found the same near-tie on nausea and more serious adverse events on tirzepatide (5% to 7% against 3%). Both trials were sponsored by Lilly, which makes tirzepatide, and SURMOUNT-5 was open-label. How the two compare on weight is on the tirzepatide vs semaglutide page.
Semaglutide against liraglutide. STEP 8 found gastrointestinal events almost equally common (84.1% against 82.7%) but twice as many people stopping daily liraglutide as weekly semaglutide, for any reason. The trial's abstract does not break that down by adverse events alone; the older drug also produced far less weight loss (−6.4% against −15.8%).
Semaglutide against dulaglutide. SUSTAIN 7 compared two pairs of doses. At the lower pair semaglutide had more gastrointestinal events (43% against 33%); at the higher pair dulaglutide had slightly more (48% against 44%). Its comparison of the two brands is on Trulicity vs Ozempic.
Orforglipron against oral semaglutide. ACHIEVE-3 is the clearest difference in the set: more gastrointestinal events on orforglipron at both doses, twice the rate of stopping for adverse events, and a larger rise in pulse (3.7 and 4.7 beats per minute against 1.0 and 1.5). It was a trial in type 2 diabetes at diabetes doses; the weight-management versions, Foundayo and the Wegovy pill, have not been compared directly, which we cover in Foundayo vs Wegovy pill.
The labels' discontinuation figures
A weaker comparison, but the one most people can check: how many people in each label's weight trials stopped permanently because of adverse reactions, against placebo in the same trials.
| Label (weight management) | Stopped on drug | Stopped on placebo | Gap |
|---|---|---|---|
| Wegovy tablets 25 mg (one trial) | 6.9% | 5.9% | 1.0 |
| Zepbound 5 / 10 / 15 mg | 4.8% / 6.3% / 6.7% | 3.4% | 1.4–3.3 |
| Wegovy injection 2.4 mg (three trials) | 6.8% | 3.2% | 3.6 |
| Wegovy injection 2.4 / 7.2 mg (two trials) | 5% / 5% | 2% | 3 |
| Foundayo 5.5 / 9 / 17.2 mg | 6% / 9% / 10% | 3% | 3–7 |
| Saxenda 3 mg | 9.8% | 4.3% | 5.5 |
"Gap" is our arithmetic. The Wegovy tablets figure has the smallest gap, but its placebo rate is unusually high (5.9%), and it comes from a single trial of about 300 people. Saxenda, the one daily injection, has the largest — consistent with STEP 8. None of these rows is a head-to-head result.
The side effects that differ by drug
Most of what these medicines cause is shared: nausea, diarrhoea, vomiting, constipation, and the same class warnings on the pancreas, gallbladder and thyroid. A few entries are specific to one label and matter more than a percentage-point difference in nausea:
- Skin sensations on high-dose Wegovy. Dysesthesia — burning, tingling or sensitive skin — was reported by 22% on Wegovy 7.2 mg against 6% on 2.4 mg and none on placebo. It is the steepest dose gradient on any GLP-1 label, set out on the dose and side effects page.
- Injection-site reactions on Zepbound, 6% to 8% against 2% on placebo. The tablets have none, by definition.
- Heart rate. Foundayo raised resting heart rate by 4 to 5 beats per minute against 0.5 on placebo, and 3% reported tachycardia against 0.9%. Zepbound's label gives 1 to 3 beats per minute, the Wegovy injection's 1 to 4.
- Low blood sugar is a small risk on these drugs alone and a real one when a GLP-1 is combined with insulin or a sulfonylurea, which the diabetes labels count separately.
- The daily routine. The tablets carry their own conditions — the Wegovy pill must be taken fasting with limited water, Foundayo need not — which some people experience as a burden and others as none; the rules are on the GLP-1 pill vs injection page.
The variable nobody ranks: dose
Across every label that prints doses, gastrointestinal side effects are lower at lower doses and concentrate during dose escalation (our nausea page sets out the timing). In practice, the dose a person reaches and how quickly they get there may matter as much as which molecule they are on. The label schedules are on the titration schedules page. The trade-off is stated plainly in the same tables: lower doses also produce less weight loss.
What this page cannot tell you
- Which drug one person will tolerate. Trial averages do not predict an individual's response.
- Anything about compounded or research versions. None of these figures applies to products that were not the ones tested.
- A ranking of the whole class. The trial that would produce one has not been run.
Sources
- SURMOUNT-5, posted results — ClinicalTrials.gov NCT05822830, adverse events and participant flow, read 2026-09-26; Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med 2025 — PubMed 40353578.
- Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med 2021 — PubMed 34170647.
- Rubino DM, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes (STEP 8). JAMA 2022 — PubMed 35015037.
- Pratley RE, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7). Lancet Diabetes Endocrinol 2018 — PubMed 29397376.
- Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3). Lancet 2026 — PubMed 41765029.
- WEGOVY (semaglutide) injection and tablets prescribing information, Novo Nordisk, SPL effective 2026-06-18 — DailyMed, sections 5.9 and 6.1.
- ZEPBOUND (tirzepatide) prescribing information, Eli Lilly, effective 2026-08-28 — DailyMed, section 6.1.
- FOUNDAYO (orforglipron) prescribing information, Eli Lilly, effective 2026-07-29 — DailyMed, section 6.1.
- SAXENDA (liraglutide) prescribing information, Novo Nordisk, effective 2026-02-25 — DailyMed, section 6.1.