Tirzepatide clinical trials: what we've learned about Mounjaro

Unless you're a medical researcher, it might feel as if injectable weight loss medications popped into existence out of thin air.

One moment, people are working hard to lose weight through diet and exercise alone. Next, we have access to game-changing injectable medications like Mounjaro (tirzepatide) and Wegovy (semaglutide) – and for thousands, losing weight seems simpler than ever.

However, the truth is that all new drugs must go through extensive clinical trials before they can be approved or sold. This is so we can study how the drugs affect patients, and decide whether they're safe and effective enough to recommend as treatments.

Mounjaro and Wegovy are no exception. The first major Mounjaro trial, for instance, took place in 2019.¹ However, the drug wasn't approved for type 2 diabetes in the US until 2022.² Its approval as a weight loss treatment came even later, in November 2023.³

And while the medications are now firmly established and widely used, we're still learning more about their potential benefits. Several ongoing Mounjaro trials, for example, are exploring the drug's effects on lifespan, body weight maintenance and more.

In this guide, we look at the key tirzepatide clinical trials and reflect on what they taught – and are teaching us – about this revolutionary medication.

The key clinical trials for Mounjaro

The SURPASS programme: evaluating tirzepatide as a type 2 diabetes treatment

SURPASS was the phase 3 clinical trial programme looking at Mounjaro as a treatment for blood sugar control in adults living with type 2 diabetes. A phase 3 trial is the final research phase before a drug is approved.

The core SURPASS tirzepatide trials began in 2019⁴ and were completed in 2021.⁵ Supplementary studies are ongoing – more on these below.

Here are the core trials and what they taught us:

• SURPASS-1: this trial tested three doses of tirzepatide against placebo (a dummy drug) in adults with type 2 diabetes. It found that the drug significantly improved blood sugar control⁶ and laid the groundwork for its approval.
  
  
• SURPASS-2: the second trial compared the effects of tirzepatide and semaglutide for blood sugar control, finding that tirzepatide was more effective.⁷
  
  
• SURPASS-3: this trial compared tirzepatide against a common insulin treatment (insulin degludec). It showed that tirzepatide was more effective.⁸
  
  
• SURPASS-4: like SURPASS-3, this trial compared tirzepatide with an insulin treatment (insulin glargine). However, it specifically studied patients with type 2 diabetes and a higher risk of heart problems. As with the last trial, tirzepatide was found to be more effective.⁹
  
  
• SURPASS-5: the final core trial evaluated the effectiveness of tirzepatide when used alongside insulin glargine. The combination demonstrated significant improvements in blood sugar control.¹⁰

The SURMOUNT programme: tirzepatide trials for weight loss

Researchers already knew that similar drugs, such as Wegovy, were beneficial for weight loss as well as blood sugar control.

That's why Mounjaro's manufacturer was keen to study the drug's effectiveness as a weight loss treatment. To this end, it launched the SURMOUNT weight loss trial programme alongside the SURPASS diabetes studies.

The SURMOUNT Mounjaro trials ran from 2019¹¹ until 2024.¹² Here's what we learned:

• SURMOUNT-1: this was the main trial looking at tirzepatide as a weight loss treatment for adults living with obesity (but not diabetes). Over a 72-week treatment programme with tirzepatide, alongside lifestyle support, participants lost around 21% of their starting body weight on average.¹³
  
  
• SURMOUNT-2: the second SURMOUNT trial evaluated tirzepatide's effectiveness as an obesity treatment in adults with type 2 diabetes. Participants lost around 15% of their starting body weight on average.¹⁴
  
  
• SURMOUNT-3: the third trial examined the effects of tirzepatide as an add-on therapy after achieving weight loss through intensive lifestyle changes. Participants saw around 21% additional weight loss on average and found it easier to maintain their initial weight loss.¹⁵
  
  
• SURMOUNT-4: this trial studied long-term treatment with tirzepatide among adults who had already lost around 21% of their weight using the drug. Those who continued taking tirzepatide lost another 5.5%, while those who switched to placebo regained 14%.¹⁶
  
  
• SURMOUNT-5: the final core SURMOUNT trial compared tirzepatide and semaglutide under identical conditions. It demonstrated that tirzepatide is more effective than semaglutide, with tirzepatide users achieving 6.5% more weight loss on average.¹⁷
  
  

The SUMMIT trial: tirzepatide for heart health

Published in 2024, the SUMMIT study looked at tirzepatide's effects on heart health. It found that tirzepatide led to a lower risk of death from cardiovascular events (heart attack or stroke) and improved the health of patients with heart failure.¹⁸

Ongoing tirzepatide trials

While Mounjaro is considered safe and effective when prescribed by a medical professional, there are still unanswered questions about the drug.

The original SURMOUNT programme, for instance, only studied the effects of Mounjaro on adults living with obesity. Could tirzepatide also be a safe treatment option for adolescents?

Researchers are seeking to answer these questions – and more – in a series of ongoing studies. Here's a snapshot of what they're looking at right now.

• SURMOUNT-ADOLESCENTS: this is a series of two trials examining tirzepatide as a treatment option for adolescents living with obesity or overweight. The first is studying whether the drug is a safe and effective treatment for weight loss in this age group.¹⁹ The second looks at weight loss in conjunction with heart health.²⁰ They're projected to finish in 2029 and 2030, respectively.¹⁹ ²⁰
  
  
• SURMOUNT-MMO: this trial is looking at tirzepatide's effects on morbidity (disease) and mortality (death) rates in adults living with obesity. The researchers hope to find more evidence for Mounjaro's potential health benefits in this treatment group. The study is projected to end in October 2027.²¹
  
  
• SURMOUNT-MAINTAIN: we know that Mounjaro is highly effective for weight loss, but can it also be used long-term to maintain a healthy weight? That's the question this trial seeks to answer. We'll soon find out, because the study is projected to finish in May 2026.²²
  
  

The importance of professional support

The key Mounjaro weight loss trials all had one thing in common. Participants were given expert dietary and lifestyle support as part of their treatment.

This specialist support is crucial because Mounjaro is not a magic wand for weight loss. By controlling appetite and snack cravings, it can make losing weight feel simpler and more manageable. But as with any weight loss treatment, you still need to eat a healthy, balanced diet and exercise regularly to see the best results.

Unfortunately, this support is often lacking. Some online pharmacies more or less send you the Mounjaro pen and leave you to figure things out on your own.

That's where SemaPen is different. When you join our Mounjaro programme, you're joining a guided treatment plan created by real UK obesity experts. For you, that means:

• Simple weight monitoring with smart scales connected to the SemaPen app.
• Expert check-ins with tailored advice to help keep your health and weight on track.
• Exclusive content and lessons to help you learn healthy habits that stick.
• Clinical support from real medical professionals by email.
  
  

Thinking of joining – or switching from another Mounjaro supplier? It's easy to find out if you're eligible. Simply take our digital consultation and we'll recommend the best treatment options for you.

Sources

1. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone (SURPASS-1). Retrieved from https://clinicaltrials.gov/study/NCT03954834

2. Eli Lilly and Company (2022) FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes [press release]. Retrieved from

https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-injection-the-first-and-only-gip-and-glp-1-receptor-agonist-for-the-treatment-of-adults-with-type-2-diabetes-301547339.html

3. U.S. Food & Drug Administration (2023) FDA Approves New Medication for Chronic Weight Management [press release]. Retrieved from https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management

4. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone (SURPASS-1). Retrieved from https://clinicaltrials.gov/study/NCT03954834

5. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4). Retrieved from https://clinicaltrials.gov/study/NCT03730662

6. Rosenstock, J.R. et al. (2021) "Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial" The Lancet, 398(10295) https://doi.org/10.1016/S0140-6736(21)01324-6

7. Frías, J.P. et al. (2021) "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes" The New England Journal of Medicine, 385(6) https://doi.org/10.1056/NEJMoa2107519

8. Ludvik, B. et al. (2021) "Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial" The Lancet, 398(10300) https://doi.org/10.1016/S0140-6736(21)01443-4

9. Del Prato, S. et al. (2021) "Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial" The Lancet, 398(10313) https://doi.org/10.1016/S0140-6736(21)02188-7

10. Dahl, D. et al. (2022) "Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial" JAMA, 327(6)

https://doi.org/10.1001/jama.2022.0078

11. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1). Retrieved from https://clinicaltrials.gov/study/NCT04184622

12. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5). Retrieved from https://clinicaltrials.gov/study/NCT05822830

13. Jastreboff, A.M. et al. (2022) "Tirzepatide Once Weekly for the Treatment of Obesity" The New England Journal of Medicine, 387(3) https://doi.org/10.1056/NEJMoa2206038

14. Garvey, T. et al. (2023) "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial" The Lancet, 402(10402) https://doi.org/10.1016/S0140-6736(23)01200-X

15. Wadden, T.A. et al. (2023) "Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial" Nature Medicine, 29:2909-2918 https://doi.org/10.1038/s41591-023-02597-w

16. Aronne, L.J. et al. (2023) "Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial" JAMA, 331(1) https://doi.org/10.1001/jama.2023.24945

17. Aronne, L.J. et al. (2025) "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity" The New England Journal of Medicine, 393(1) https://doi.org/10.1056/NEJMoa2416394

18. Packer, M. et al. (2024) "Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity" The New England Journal of Medicine, 392(5) https://doi.org/10.1056/NEJMoa2410027

19. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) Once Weekly in Adolescent Participants Who Have Obesity or Overweight With Weight-Related Comorbidities. Retrieved from https://clinicaltrials.gov/study/NCT06075667

20. National Library of Medicine (n.d.) A Study of Tirzepatide in Adolescents With Obesity and Weight-Related Comorbidities (SURMOUNT-ADOLESCENTS-2). Retrieved from https://clinicaltrials.gov/study/NCT06439277

21. National Library of Medicine (n.d.) A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity (SURMOUNT-MMO). Retrieved from https://clinicaltrials.gov/study/NCT05556512

22. National Library of Medicine (n.d) A Study of LY3298176 (Tirzepatide) For the Maintenance of Body Weight Reduction in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities. Retrieved from

https://clinicaltrials.gov/study/NCT06047548

This article was reviewed and approved by Lujain Alhassan, Bariatric Dietitian, and Sarah Abdula, Specialist Dietitian, on 5 January 2026.