Mounjaro vs. Ozempic: A Comprehensive Comparative Analysis

The increasing prevalence of type 2 diabetes and obesity has intensified the focus on effective pharmacological interventions. Among these, two injectable medications—Mounjaro (tirzepatide) and Ozempic (semaglutide)—have garnered significant attention. This comprehensive analysis explores their mechanisms of action, clinical efficacy, side effect profiles, and current availability within the United Kingdom.

Mechanisms of Action

Semaglutide, marketed as Ozempic, functions as a glucagon-like peptide-1 (GLP-1) receptor agonist. GLP-1 is an incretin hormone, part of a group of metabolic messengers secreted by the gut in response to food intake. It plays a critical role in regulating blood glucose, particularly after meals. Its key actions include:

• Stimulating glucose-dependent insulin secretion from pancreatic beta cells
• Inhibiting glucagon secretion, which otherwise raises blood sugar
• Slowing gastric emptying, which delays the absorption of glucose
• Promoting satiety via central nervous system signalling

The role of GLP-1 was uncovered in the 1980s during research into the incretin effect—the observation that oral glucose stimulated more insulin than intravenous glucose. This led to the identification of GLP-1 as a key player in postprandial glucose regulation. While natural GLP-1 is quickly broken down, synthetic analogues like semaglutide have been developed with extended half-lives to make once-weekly dosing possible.

Tirzepatide, marketed as Mounjaro, builds on this by targeting two receptors: GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).

GIP was first discovered in the early 1970s and originally named gastric inhibitory polypeptide due to its suspected role in reducing stomach acid. However, further research found it primarily stimulated insulin secretion in a glucose-dependent manner, prompting its renaming. GIP is released by K cells in the small intestine after nutrient intake and has additional roles in:

• Lipid metabolism
• Fat storage regulation
• Energy homeostasis

By activating both GLP-1 and GIP receptors, tirzepatide may provide synergistic benefits, including improved glycaemic control, enhanced satiety, and greater weight loss.

Efficacy

Type 2 Diabetes

SURPASS-2 Trial

A direct comparison between tirzepatide and semaglutide in the SURPASS-2 trial demonstrated:

• HbA1c reduction:
  • Tirzepatide (15 mg): up to 2.3%
  • Semaglutide (1 mg): 1.9%
• Average weight loss:
  • Tirzepatide: 5.5 kg
  • Semaglutide: 3.8 kg

Meta-Analysis Findings

A meta-analysis of multiple trials confirmed tirzepatide’s superiority:

• 5 mg dose: 1.5× higher odds of achieving ≥5% weight loss than semaglutide
• 10 mg dose: 3.0× higher odds
• 15 mg dose: 4.2× higher odds

However, higher tirzepatide doses also led to slightly higher discontinuation rates due to gastrointestinal side effects.

Renal Outcomes

Tirzepatide has also shown early signs of kidney protection, with slower decline in eGFR and reduced progression of proteinuria, although more dedicated studies are needed to confirm long-term renal outcomes.

Obesity

SURMOUNT-1 Trial

In adults with obesity (without diabetes):

• Tirzepatide (15 mg): 20.9% average body weight reduction over 72 weeks
• Semaglutide (2.4 mg) (based on STEP trials): ~14.9% average reduction

STEP 5 Long-Term Results

Semaglutide also demonstrated durable effects:

• At 104 weeks, patients maintained ~15% weight loss on semaglutide 2.4 mg (STEP 5)

SELECT Trial – Cardiovascular Benefit

Semaglutide significantly reduced major adverse cardiovascular events by 20% in people with obesity and pre-existing heart disease—indicating benefit beyond weight loss.

Diabetes Prevention

Notably, in SURMOUNT-1, tirzepatide reduced the progression from prediabetes to type 2 diabetes by 94% compared to placebo, suggesting strong preventive potential.

Side Effect Profiles

Both medications share a similar side effect profile, primarily gastrointestinal in nature:

• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Appetite loss

These effects are typically dose-dependent and transient, most common during the dose-escalation period. In trials, up to 50–60% of users experienced some GI symptoms, though only 4–8% discontinued treatment as a result.

Emerging reports have flagged rare visual disturbances, including non-arteritic anterior ischaemic optic neuropathy (NAION) in some users of GLP-1 agonists. These links are still under investigation, but patients should be advised to report any sudden vision changes.

Real-World Insights from Our Community Survey

To supplement the clinical data, we've launched The Mounjaro Real-World Survey — an anonymous, ongoing community survey hosted right here on our blog.

Why it matters:

• Clinical trials are controlled and selective.
• Real-life use includes a broader population with diverse health backgrounds.
• Our survey helps track emerging trends, side effects, and quality of life outcomes from actual users.

This project aims to make the Mounjaro experience more transparent, and more reflective of what people experience outside of clinical settings.

🛡️ It’s 100% anonymous
📢 Results will be published regularly here and across our social media channels
📊 Every submission helps build a clearer picture of real-world usage

👉 Click here to take part in the Mounjaro Real-World Study

Availability in the United Kingdom

Both medications are now NICE-approved in the UK:

• Semaglutide (Ozempic/Wegovy): Approved for managing type 2 diabetes and for weight loss in adults with BMI ≥ 35 kg/m² and a weight-related comorbidity
• Tirzepatide (Mounjaro): Approved in December 2024 under similar criteria

However, availability is limited due to NHS capacity and rollout strategy:

• Mounjaro is currently prescribed only through specialist Tier 3 weight management services.
• NHS England estimates only 220,000 patients will have access to Mounjaro over the next three years, despite high demand.

Conclusion

Both Mounjaro and Ozempic represent significant strides in obesity and diabetes care. While both are effective, tirzepatide appears to offer more robust outcomes in terms of weight loss and glycaemic control, likely due to its dual mechanism.

However, individual response, side effects, and access will continue to shape treatment decisions. Real-world feedback—like the results from our community survey—will play a vital role in helping people make informed choices.

As always, treatment decisions should be made in consultation with a qualified medical professional.

Disclaimer

This article is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Always consult with a qualified healthcare provider regarding any medical concerns or before starting a new medication.