The evidence reveals clear differences in effectiveness at the time of comparing tirzepatide vs semaglutide for weight loss. Recent studies show that tirzepatide (Mounjaro) helps patients lose substantially more weight. Patients lost an average of 20.2% of their body weight with Mounjaro compared to 13.7% with semaglutide (Wegovy).
Clinical trials paint an even more impressive picture. Patients taking Mounjaro’s highest dose lost up to 22.5% of their starting weight over 72 weeks. The results also showed that tirzepatide users’ waist measurements decreased by about 5cm (2 inches) more than semaglutide users. Both medications proved effective, and more than 89% of Mounjaro’s users shed at least 5% of their starting weight. The differences between these treatments go beyond simple weight loss results.
This piece will get into how Wegovy and Mounjaro stack up against each other. We’ll explore their mechanisms of action, possible side effects, and what they cost. You’ll find complete information here to make an informed decision, whether you’re thinking about taking these medications or just want to understand how they differ.
How Tirzepatide and Semaglutide Work in the Body
The main difference between tirzepatide and semaglutide comes from how they target different receptors in the body. Their mechanisms explain why they work differently.
Hormonal Mechanism: GLP-1 vs GLP-1 + GIP
Semaglutide (Wegovy) acts only as a GLP-1 receptor agonist. It mimics the body’s natural hormone to control blood sugar and reduce appetite. Semaglutide shares 94% similarity with human GLP-1 and activates GLP-1 receptors. This activation improves insulin secretion based on glucose levels.
Tirzepatide (Mounjaro) works differently as a dual-action “twincretin.” It targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. This dual action gives tirzepatide unique properties. It matches the body’s natural GIP sensitivity but shows five times less sensitivity to GLP-1R compared to natural GLP-1.
Appetite Suppression and Satiety Signals
These medications control appetite through different pathways. Semaglutide works on the brain’s satiety centres and interacts with leptin, which regulates hunger. Food stays in your stomach longer, making you feel full.
Tirzepatide’s dual action creates stronger appetite suppression. Studies show that activating both GLP-1 and GIP receptors boosts pro-opiomelanocortin gene expression, which reduces hunger better. Scientists have found specific neurons in the hypothalamus that only respond when both GLP-1 and GIP are stimulated.
Impact on Blood Sugar and Fat Metabolism
Tirzepatide shows better results in improving insulin sensitivity – 65.7% compared to semaglutide’s 37.5%. This higher insulin sensitivity helps tirzepatide control glucose levels better.
Both medications help with fat metabolism. Semaglutide turns white fat (storage) into brown fat (calorie-burning). It also lowers triglycerides and LDL cholesterol levels.
Tirzepatide’s GIP component brings extra metabolic benefits. It helps white adipose tissue handle fats better after meals and makes fat tissue more sensitive to insulin. This might prevent fat from building up in the wrong places.
Weight Loss Results: Clinical Trials and Real-World Data
Clinical trials show remarkable differences in weight loss results between these medications.
SURMOUNT-1 vs STEP-1: 22.5% vs 17% Weight Loss
The groundbreaking SURMOUNT-1 trial showed tirzepatide’s exceptional results. Participants lost an average of 22.5% weight at the 15mg dose over 72 weeks. Semaglutide users in STEP-1 lost about 15% of their body weight at the 2.4mg dose. The numbers tell an impressive story – 39.7% of people taking tirzepatide dropped at least 25% of their starting weight. Only 4.9% of semaglutide users achieved similar results.
JAMA 2024 Study: 15.3% vs 8.3% at 12 Months
Real-life evidence backs up these clinical findings. A 2024 JAMA study with 18,386 matched patients revealed striking differences. Tirzepatide users lost 15.3% of their weight at 12 months while semaglutide users lost 8.3%. These results show tirzepatide works almost twice as well in everyday clinical practise. People started seeing differences quickly – within 3 months, tirzepatide users lost 5.9% compared to 3.6% with semaglutide.
Waist Circumference Reduction: 5cm Greater with Tirzepatide
Scale weight isn’t the only benefit. Tirzepatide leads to better waist circumference reduction, which helps track visceral fat. SURMOUNT-5 patients’ waist measurements dropped by 18.4cm with tirzepatide and 13cm with semaglutide – a crucial 5.4cm difference. This matters because every 5cm increase in waist size leads to a 7-9% higher mortality risk.
Effectiveness in Non-Diabetic vs Diabetic Patients
The results stand out more in people without diabetes. Non-diabetic patients lost 7% of their weight with tirzepatide compared to 3.4% with semaglutide. The gap narrows for diabetic patients though – they lost 3.3% with tirzepatide versus 2.2% with semaglutide. Different groups might respond uniquely to these medications.
Side Effects: What to Expect from Each Drug
Tirzepatide and semaglutide show similar side effects, but patients should think over some key differences between them.
Gastrointestinal Issues: Nausea, Diarrhoea, Constipation
These medications primarily cause gastrointestinal symptoms. Nausea affects up to 22% of tirzepatide users compared to 18% with semaglutide. Patients on tirzepatide experience diarrhoea at rates of 12-22%, while semaglutide users report 12%. The good news is these symptoms usually peak during dose adjustments and fade over time.
Discontinuation Rates: 6% vs 8%
The medications show slight variations in treatment dropouts due to side effects. Research data reveals discontinuation rates of 6.0% for tirzepatide 5mg, 8.5% for tirzepatide 10mg and 15mg, compared to 4.1% for semaglutide. Early dropouts due to side effects happen more often than late ones (21.0% vs 8.7%).
Serious Adverse Events: Pancreatitis, Gallbladder Disease
Serious complications, though rare, need attention. GLP-1 agonist use relates to higher risks of pancreatitis (adjusted HR: 9.09), bowel obstruction (HR: 4.22), and gastroparesis (HR: 3.67). Gallbladder problems occur with both medications, but tirzepatide users develop fewer gallstones.
Long-Term Safety and Black Box Warnings
FDA “black box” warnings exist for both medications due to thyroid tumours found in animal studies. UK regulatory data shows 18 deaths linked to tirzepatide and 29 to semaglutide. A full picture of risks versus benefits remains crucial, especially for weight loss patients, as these problems are systemic.
Cost Breakdown and Accessibility
The cost of weight management medications shapes treatment decisions in meaningful ways.
Annual Cost: £3,277.64 (Mounjaro) vs £2,147.65 (Wegovy)
Private prescription costs show a clear gap between these medications. Tirzepatide (Mounjaro) costs about £3,277.64 per year, while semaglutide (Wegovy) costs £2,147.65. Many patients need long-term treatment, and this £1,130 yearly difference affects their choice of medication.
Dose-by-Dose Price Comparison
Wegovy starts at lower prices. You can get the Wegovy starter dose (0.25mg) for £99-£129.99, while Mounjaro’s lowest dose (2.5mg) ranges from £148.99. The price difference gets smaller as treatment continues but stays noticeable:
Wegovy maintenance (2.4mg): £189-£210 Mounjaro maintenance (15mg): £300-£370
Insurance Coverage and NHS Availability
NHS keeps strict limits on both medications. Patients need a BMI ≥40 (or ≥37.5 for certain ethnic groups) and at least four weight-related conditions to qualify. Private medical insurance plans don’t cover weight management medications because they see obesity as a lifestyle condition rather than an acute illness.
Support Programmes and Online Prescriptions
These medications come with required “wraparound care” programmes that focus on diet, physical activity, and lifestyle changes. Online pharmacies offer another option through private prescriptions, with prices that vary among providers. Patients who can’t get NHS treatment often pay high out-of-pocket costs, even though these medications work well.
Comparison Table
| Comparison Factor | Tirzepatide (Mounjaro) | Semaglutide (Wegovy) |
| Average Weight Loss | 20.2% of body weight | 13.7% of body weight |
| Maximum Weight Loss (72 weeks) | 22.5% | 17% |
| Real-life Weight Loss (12 months) | 15.3% | 8.3% |
| Mechanism of Action | Dual-action “twincretin” (GLP-1 + GIP receptors) | Single-action GLP-1 receptor agonist |
| Insulin Sensitivity Improvement | 65.7% | 37.5% |
| Waist Circumference Reduction | 18.4cm | 13cm |
| Common Side Effects Rate | Nausea (22%), Diarrhoea (12-22%) | Nausea (18%), Diarrhoea (12%) |
| Treatment Discontinuation Rate | 6.0% (5mg), 8.5% (10mg & 15mg) | 4.1% |
| Annual Cost | £3,277.64 | £2,147.65 |
| Maintenance Dose Cost | £300-£370 (15mg) | £189-£210 (2.4mg) |
| Starting Dose Cost | £148.99-£199 (2.5mg) | £99-£129.99 (0.25mg) |
| Patients Losing ≥25% Body Weight | 39.7% | 4.9% |
Conclusion
Research shows tirzepatide works better than semaglutide to manage weight. People who use tirzepatide lose about 20.2% of their body weight, while semaglutide users lose 13.7%. They also see better results in waist size and insulin sensitivity. This difference comes from how tirzepatide targets both GLP-1 and GIP receptors, while semaglutide only works on GLP-1 receptors.
These medications have similar side effects, mostly affecting the digestive system. Nausea affects more people using tirzepatide (22% vs 18%), but few people stop taking either medication. The rare serious side effects need careful attention before starting treatment.
The cost between these options is a big deal as it means tirzepatide costs £3,277.64 per year compared to semaglutide’s £2,147.65. This £1,130 yearly difference might limit who can get these medications, especially since both are not widely available on the NHS.
Your choice between tirzepatide and semaglutide depends on your situation. If getting the best possible weight loss results matters most to you, tirzepatide might be worth the extra money, especially when you have a lot of weight to lose. But if you’re on a budget or need less help with weight loss, semaglutide could be the right choice at a lower price.
Both medications have reshaped the scene of weight management. All the same, they work best with lifestyle changes rather than replacing them. You should talk to your doctor before starting either medication to check if it’s right for you based on your health history, weight loss goals, possible side effects, and budget.
