Mounjaro vs Wegovy: Which Is Better for Weight Loss?

Both are weekly injections. Both are clinically proven to produce significant weight loss. But Mounjaro and Wegovy work differently, carry different evidence profiles, and suit different patients. This is an honest, clinical comparison, not a marketing exercise, written to help you understand which medication may be more appropriate for you.

The short answer

Mounjaro produces greater average weight loss in clinical trials. Wegovy is the only weight loss medication with a licensed cardiovascular indication. For most patients without significant heart disease, Mounjaro is the more potent option. For those with established cardiovascular disease, Wegovy's SELECT trial evidence is clinically decisive.

How they work differently

Wegovy contains semaglutide, a GLP-1 receptor agonist. It suppresses appetite, slows gastric emptying, and improves insulin sensitivity, all by mimicking a single gut hormone.

Mounjaro contains tirzepatide, a dual GLP-1 and GIP receptor agonist. It does everything semaglutide does, plus activates GIP receptors, which promote fat metabolism, regulate energy balance, and enhance the appetite-suppressing effects of GLP-1.

What the clinical evidence shows

SURMOUNT-1 (NEJM 2022, n=2,539, 72 weeks)

Average weight loss with tirzepatide: 5mg = 16%, 10mg = 21.4%, 15mg = 22.5%. At the highest dose, 36.2% of patients lost 25% or more of their body weight. Placebo group: 2.4%.

STEP-1 (NEJM 2021, n=1,961, 68 weeks)

Average weight loss with semaglutide 2.4mg: 14.9%. Half of all patients lost 15% or more. Placebo group: 2.4%.

SURMOUNT-5, the first direct head-to-head (NEJM 2025, Aronne et al, n=751, 72 weeks)

This was the first randomised controlled trial to directly compare tirzepatide against semaglutide in adults with obesity but without diabetes. The results were unambiguous:

• Tirzepatide: 20.2% average weight loss
• Semaglutide: 13.7% average weight loss
• Estimated treatment difference: −6.5 percentage points (95% CI −8.1 to −4.9, P<0.001)
• Achievement of ≥25% weight loss: 31.6% (tirzepatide) vs 16.1% (semaglutide)
• GI-related discontinuations: 2.7% (tirzepatide) vs 5.6% (semaglutide)

Conclusion: tirzepatide demonstrated superior weight loss to semaglutide at 72 weeks, the first direct clinical confirmation of what cross-trial comparisons had suggested.

"SURMOUNT-5, published in the New England Journal of Medicine in 2025, provided the first direct head-to-head evidence: tirzepatide produced 47% greater relative weight loss than semaglutide in adults with obesity over 72 weeks."

Wegovy's newer 7.2mg dose narrows the gap. In the STEP UP trial, the higher 7.2mg dose reached up to around 21% average weight loss (about 18.7% on a treatment-policy basis), while the standard 2.4mg dose used in the head-to-head SURMOUNT-5 comparison produced around 13.7% to 15%. Mounjaro 15mg remains higher in its own trial (~22.5%), and SURMOUNT-5 still favoured tirzepatide directly.

Cardiovascular protection. Wegovy's unique advantage

The SELECT trial (NEJM 2023, Lincoff et al) demonstrated that semaglutide 2.4mg reduced major adverse cardiovascular events, heart attack, stroke, and cardiovascular death. By 20% in patients with pre-existing cardiovascular disease and a BMI of 27 or above. The MHRA has licensed Wegovy specifically for cardiovascular risk reduction.

For patients with established heart disease, Wegovy is clinically the right choice regardless of comparative weight loss data. Mounjaro's cardiovascular outcomes trial (SURMOUNT-MMO) is ongoing, with results pending.

Dosing comparison

Side effects

Both medications share a similar gastrointestinal side effect profile, nausea, diarrhoea, vomiting, and constipation, predominantly during dose escalation. SURMOUNT-5 showed that GI-related discontinuations were lower with tirzepatide (2.7%) than semaglutide (5.6%), suggesting tirzepatide may be slightly better tolerated in this respect. For both medications, side effects improve with time.

Who suits each medication?

Mounjaro may be more appropriate for

• Patients prioritising maximum weight loss
• Patients without significant cardiovascular comorbidities
• Patients with type 2 diabetes
• Patients who have previously tried Wegovy

Wegovy may be more appropriate for

• Patients with established cardiovascular disease or high CV risk
• Patients where Mounjaro is contraindicated
• Patients wanting the most mature long-term cardiovascular outcome data

Can you switch?

Yes, switching between the two is clinically straightforward. Your pharmacist can advise on dose alignment. There is no requirement to restart at the lowest dose if you are already stable on your current medication.

"The most important factor is not which drug is theoretically superior in a trial. It's which is right for you, based on your full medical history. That is exactly what our consultation is designed to assess."