Comparison
Tirzepatide vs Semaglutide
Mounjaro (tirzepatide) and Wegovy (semaglutide) are the two weight-loss injections most people in the UK are choosing between. They work in related ways, but one activates two hormone receptors and the other one — and for the first time we have a direct head-to-head trial.
Tirzepatide vs Semaglutide at a glance
| Tirzepatide | Semaglutide | |
|---|---|---|
| Receptors | GIP + GLP-1 | GLP-1 only |
| UK brands | Mounjaro | Wegovy (weight), Ozempic (diabetes) |
| Dosing | Weekly, 2.5 mg → up to 15 mg | Weekly, 0.25 mg → 2.4 mg |
| Pivotal weight trial | SURMOUNT-1: −20.9% at 72 wk (15 mg) | STEP 1: −14.9% at 68 wk (2.4 mg) |
| Head-to-head (SURMOUNT-5) | −20.2% at 72 weeks | −13.7% at 72 weeks |
| Cardiovascular outcome data | SURMOUNT-MMO ongoing | SELECT: 20% fewer major CV events |
| Most common side effects | Nausea, diarrhoea, constipation | Nausea, diarrhoea, constipation |
How they work
Tirzepatide
GLP-1 receptor activation slows stomach emptying and signals fullness to the brain. GIP receptor activation was once expected to work against weight loss, but tirzepatide showed the combination produces more appetite suppression and better insulin sensitivity than GLP-1 activation alone. The peptide is built on the GIP sequence and modified with a C20 fatty-diacid chain that binds albumin, giving the five-day half-life.
Semaglutide
Native GLP-1 is cleared within minutes. Semaglutide survives for a week because of two changes: an amino-acid swap that blocks the DPP-4 enzyme, and a C18 fatty-diacid chain that binds albumin. Once active at the GLP-1 receptor it boosts glucose-dependent insulin release, suppresses glucagon, slows gastric emptying and — most importantly for weight — acts on appetite centres in the brain to reduce hunger and food cravings.
Side effects compared
Tirzepatide
- Gastrointestinal: nausea, diarrhoea, constipation, vomiting and indigestion — most common in the first weeks after each dose increase.
- Reduced appetite, burping, abdominal pain, fatigue.
- Less common but serious: gallbladder problems, pancreatitis, severe dehydration from vomiting/diarrhoea.
- The MHRA has warned that Mounjaro may reduce the effectiveness of oral contraceptives in people who are overweight, particularly after starting and after each dose increase.
Carries the class warning about thyroid C-cell tumours seen in rodents; it is not used in people with a personal or family history of medullary thyroid cancer.
Semaglutide
Wegovy side effects are among the most-searched questions about the drug. In STEP trials:
- Very common: nausea (about 44% on 2.4 mg), diarrhoea, vomiting, constipation, abdominal pain, headache, fatigue.
- Common: indigestion, burping, bloating, dizziness, hair thinning during rapid weight loss, gallstones.
- Rare but serious: acute pancreatitis, gallbladder inflammation, worsening diabetic retinopathy in people with existing eye disease.
Most GI symptoms are mild-to-moderate and settle within weeks of each dose step. Rodent studies showed thyroid C-cell tumours; the relevance to humans is unknown, but the drug is not used with a history of medullary thyroid cancer.
Bottom line
On weight loss alone, tirzepatide came out ahead in SURMOUNT-5, with about 47% more relative weight reduction. Semaglutide has the longer track record and proven cardiovascular benefit from SELECT. GI side effects are similar in type for both. Which is appropriate for a person is a prescriber's decision.
Frequently asked questions
What is the main difference between Tirzepatide and Semaglutide?
Receptors: Tirzepatide — GIP + GLP-1; Semaglutide — GLP-1 only.
Is Tirzepatide or Semaglutide licensed in the UK?
Tirzepatide is licensed in the UK as Mounjaro. Semaglutide is licensed in the UK.