Picture 2,539 people living with obesity or overweight. They all get the same advice: eat less and move more. Some of them also receive a new medication once a week, while the rest get a placebo. After 72 weeks, the results are in.
People on placebo lost an average of 3% of their body weight. People who received the new drug at the highest dose studied lost almost 21%. And more than half of them lost a fifth of their body weight or more.
That was the SURMOUNT-1 trial, and the drug is called tirzepatide. It has since been approved in the United States and the European Union, and it has moved to the center of the debate about how obesity and diabetes should be treated today. Let's look at what it actually is, why it works so well and what we know about it from large clinical trials.
The Signals Your Body Sends After Every Meal
To understand tirzepatide, we have to start with something that happens inside you several times a day without you even noticing: eating.
As soon as you eat and food reaches your gut, the gut releases a group of hormones into the blood called incretins. Their job is to prepare the body for the incoming nutrients. The two most important ones are:
- GLP-1, which prompts the pancreas to release insulin, slows down stomach emptying and sends a “that's enough” signal to the brain.
- GIP, which also increases insulin release after meals and plays a role in how the body handles fat.
Both hormones lower blood sugar mainly when it's elevated, that is, after a meal. That matters, because it means they work in a smart, targeted way.
Medicine started mimicking these signals years ago. Drugs were developed that copy the hormone GLP-1, the best known of which is semaglutide. GIP, however, was long left on the sidelines, because less was known about its benefits for treatment.
Then scientists at Eli Lilly asked a question: what if we didn't mimic just one of these signals, but both at once?
One Molecule, Two Keys
The result was tirzepatide. It's a peptide, a chain of 39 amino acids, and it's the first approved drug to activate the receptors for both hormones at the same time. Scientifically, it's called a dual GIP and GLP-1 receptor agonist. It's sold under the brand names Mounjaro and Zepbound.
The way the molecule was built is interesting. It's based on the GIP hormone, which scientists modified so that it could also bind to the GLP-1 receptor. So while older drugs press one button, tirzepatide presses two at once.
There was one more catch, though. Natural incretins break down in the body within a few minutes. So the scientists attached a fatty acid to the molecule. This makes tirzepatide bind to a blood protein called albumin, which protects it from rapid breakdown. As a result, it stays in the body for about five days and only needs to be given once a week.
What Happens in the Body When Tirzepatide Works
According to the European Medicines Agency (EMA), tirzepatide mimics both gut hormones. In practice, this has three effects that complement each other:
- The pancreas releases more insulin after meals, so blood sugar levels drop.
- Feeling full comes sooner and lasts longer. People naturally eat less without having to fight hunger.
- The stomach empties more slowly, so food stays there longer and the feeling of fullness is extended.
The result is better blood sugar control and gradual weight loss. That's why tirzepatide addresses two very common conditions at once: type 2 diabetes and obesity.
The First Test: Type 2 Diabetes
Before tirzepatide made it to obesity treatment, it had to prove itself in diabetes. At the end of 2018, a clinical trial program called SURPASS began. Its five main international trials included roughly 6,000 people with type 2 diabetes and lasted 40 to 52 weeks. Tirzepatide was tested against placebo, insulins and semaglutide.
The main measure was HbA1c (glycated hemoglobin), which reflects average blood sugar over roughly the past three months. It's the value doctors watch most closely in people with diabetes.
- According to the manufacturer, HbA1c fell by an average of 1.7 to 2.4 percentage points across the individual trials.
- In SURPASS-2, published in 2021 in the New England Journal of Medicine, tirzepatide went head-to-head with semaglutide for the first time. At every dose studied, it lowered both HbA1c and body weight more.
- People with diabetes lost an average of about 5 to 11 kilograms (roughly 12 to 25 pounds), even though weight loss wasn't the main goal of these trials.
In May 2022, the US Food and Drug Administration (FDA) approved tirzepatide under the name Mounjaro to treat type 2 diabetes. The European Union approved it in September of the same year.
A Fifth of Body Weight: The SURMOUNT-1 Trial
Then came the trial we described at the beginning. SURMOUNT-1 was published in 2022 in the New England Journal of Medicine and focused on people with obesity or overweight who did not have diabetes.
Let's take a closer look at the numbers:
- At the highest dose studied, participants lost an average of 20.9% of their body weight. On placebo, it was 3.1%.
- 56.7% of people on the highest dose lost a fifth of their body weight or more. Only 3.1% of people on placebo achieved this.
- Even the lowest dose studied led to an average weight loss of around 15%.
To put that in perspective: someone who started at 110 kilograms (about 240 pounds) would lose roughly 22 kilograms (nearly 50 pounds) with a 20% reduction.
In November 2023, the FDA approved tirzepatide under the name Zepbound for chronic weight management. It's intended for adults with a body mass index (BMI) of 30 or higher, or 27 or higher if they also have a weight-related health condition such as high blood pressure, type 2 diabetes or sleep apnea. In the European Union, it's used for weight management under the same name as for diabetes: Mounjaro.
Clash of the Champions: Tirzepatide vs. Semaglutide
After these results, one question hung in the air for doctors and patients alike: is tirzepatide really better than semaglutide, the best-known drug based on GLP-1 alone? The answer came from SURMOUNT-5, published in 2025 in the New England Journal of Medicine.
This time, it wasn't a comparison with placebo but a direct head-to-head. 751 adults with obesity and without diabetes were split into two groups. One received tirzepatide, the other semaglutide, each at the highest dose the participant tolerated well. The trial lasted 72 weeks.
| Tirzepatide | Semaglutide | |
|---|---|---|
| Average weight loss | 20.2% | 13.7% |
| Average weight loss in kilograms | 22.8 kg | 15.0 kg |
| Reduction in waist circumference | 18.4 cm | 13.0 cm |
Tirzepatide came out ahead on every measure. One interesting detail was the difference between the sexes: in both groups, men lost about 6% less weight than women. Men made up 35% of participants, more than in earlier obesity trials, which according to the authors may explain why average weight loss was slightly lower than in SURMOUNT-1.
Three Years Later: The Diabetes That Never Came
Some of the participants in SURMOUNT-1 had prediabetes at the start, meaning slightly elevated blood sugar that is a precursor to diabetes. These people (more than a thousand participants) continued treatment for a total of 176 weeks, more than three years. The results were published in late 2024 in the New England Journal of Medicine.
- People on the highest dose studied maintained a weight loss of around 20% even after three years.
- Type 2 diabetes developed in only 2.4% of people treated with tirzepatide, compared with 13.7% on placebo. That corresponds to a risk reduction of about 94%.
The study also delivered an important lesson. After treatment was stopped, weight, blood sugar and blood pressure began returning to their original levels within 17 weeks. Obesity behaves like other chronic conditions, such as high blood pressure: as long as it's treated, it's under control, but it doesn't go away on its own.
Better Nights: The First Drug for Sleep Apnea
December 2024 brought another milestone. The FDA approved tirzepatide (Zepbound) to treat moderate to severe obstructive sleep apnea in adults with obesity. It was the first drug ever approved for this condition.
Sleep apnea is a condition in which the airways repeatedly narrow or close during sleep, causing breathing to stop for a moment. People with it often wake up tired without knowing why. Obesity is one of its main risk factors.
In the SURMOUNT-OSA trials, tirzepatide reduced the number of breathing interruptions per hour of sleep by about 25, compared with about 6 on placebo.
Timeline: From the Lab to the Doctor's Office
| Year | What happened |
|---|---|
| 2018 | Eli Lilly scientists describe a new molecule, then known as LY3298176, in the journal Molecular Metabolism. At the end of the year, the SURPASS trial program begins. |
| 2021 | SURPASS-2 in NEJM: tirzepatide lowers HbA1c and body weight more than semaglutide. |
| 2022 | May: the FDA approves Mounjaro for type 2 diabetes. June: SURMOUNT-1 shows an average weight loss of 20.9%. September: approval in the European Union. |
| 2023 | November: the FDA approves Zepbound for chronic weight management. |
| 2024 | Three-year SURMOUNT-1 data: diabetes risk about 94% lower in people with prediabetes. December: the FDA approves Zepbound for obstructive sleep apnea. |
| 2025 | SURMOUNT-5: in a head-to-head trial, 20.2% weight loss with tirzepatide vs. 13.7% with semaglutide. |
Why Tirzepatide Is Getting So Much Attention
- It showed the power of combination. Combining two hormones in one molecule delivered results that weight-loss drugs had never achieved before.
- It brought GIP back into the game. The hormone long stood in the shadow of GLP-1, but tirzepatide showed it has a place in treatment.
- It tackles several problems at once. Type 2 diabetes, obesity and, in people with obesity, sleep apnea.
- It changed how we see obesity. The trial results strengthened the view of obesity as a chronic disease that can be treated effectively, not just a matter of willpower.
- It opened the door to other drugs. Its success has spurred the development of new molecules that combine multiple hormonal signals.
Frequently Asked Questions
What exactly is tirzepatide?
A peptide made up of 39 amino acids that mimics two gut hormones: GIP and GLP-1. It helps the body manage blood sugar better and reduces appetite.
What's the difference between Mounjaro and Zepbound?
They contain the same active ingredient, tirzepatide. In the US, Mounjaro is used to treat type 2 diabetes, and Zepbound to treat obesity and sleep apnea. In the European Union, tirzepatide is authorized under the name Mounjaro for both uses: diabetes and weight management.
What's the difference between tirzepatide and semaglutide?
Semaglutide mimics only one hormone, GLP-1. Tirzepatide mimics two, GLP-1 and GIP. In a direct comparison in the SURMOUNT-5 trial, tirzepatide led to greater weight loss (20.2% vs. 13.7%).
Why is tirzepatide only given once a week?
A fatty acid is attached to the molecule, which makes it bind to the blood protein albumin. This protects it from rapid breakdown, so it stays in the body for about five days.
What happens when treatment stops?
According to three-year data from SURMOUNT-1, weight, blood sugar and blood pressure began returning to their original levels after treatment was stopped. That's why obesity treatment is considered long-term, much like treatment for high blood pressure.
What side effects have been reported in trials?
The most common were digestive issues such as nausea. According to SURMOUNT-5, they were mostly mild to moderate and occurred mainly while the dose was being gradually increased.
Does tirzepatide help people without diabetes?
Yes. Both SURMOUNT-1 and SURMOUNT-5 included people with obesity or overweight who did not have diabetes. In people with prediabetes, three-year data showed that tirzepatide also reduced the risk of developing diabetes by about 94%.
Is tirzepatide approved as a medicine?
Yes. In the United States, it's approved as Mounjaro and Zepbound. In the European Union, it's authorized under the name Mounjaro for type 2 diabetes and weight management. It's a prescription-only medicine.
What does “research use only” mean for tirzepatide?
Tirzepatide labeled “research use only” is intended for laboratory and scientific research. It is not an approved medicinal product and is not intended for human use. The only tirzepatide products approved for treatment are licensed, prescription-only medicines.
Why is a certificate of analysis important for research peptides?
A certificate of analysis (CoA) confirms that the package really contains the substance stated on the label and shows how pure it is. It usually includes the results of chromatography (HPLC), which shows purity, and mass spectrometry (MS), which confirms that it's the right molecule. Without it, research results wouldn't be reliable.
Summary
Tirzepatide started with a simple question: what if we didn't mimic just one of the signals the body sends after a meal, but two at once? Large clinical trials provided the answer. People with obesity lost an average of more than 20% of their body weight on it, people with type 2 diabetes saw major improvements in blood sugar, and in people with prediabetes, the risk of diabetes fell by about 94%. It beat semaglutide in a head-to-head trial and became the first drug approved to treat sleep apnea in people with obesity.
Tirzepatide has shifted our sense of what's possible in treating obesity and diabetes, and it has paved the way for a whole new generation of drugs based on combining hormonal signals.
You'll find an overview of tirzepatide and other research peptides on our research compounds page: tirzepatide.
Sources
- Eli Lilly and Company – press release: FDA approves Mounjaro (tirzepatide) for type 2 diabetes, May 13, 2022: investor.lilly.com
- Eli Lilly and Company – press release: FDA approves Zepbound (tirzepatide) for chronic weight management, November 8, 2023: investor.lilly.com
- European Medicines Agency (EMA) – Mounjaro, European public assessment report (EPAR): ema.europa.eu
- Coskun T, et al. Study describing the molecule LY3298176 (tirzepatide). Molecular Metabolism, 2018;18: molecularmetabolism.com
- Frías JP, et al. “Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes” (SURPASS-2). New England Journal of Medicine, 2021.
- Jastreboff AM, Aronne LJ, Ahmed NN, et al. “Tirzepatide Once Weekly for the Treatment of Obesity” (SURMOUNT-1). New England Journal of Medicine, 2022;387:205–216. Summary: acc.org
- Jastreboff AM, le Roux CW, Stefanski A, et al. “Tirzepatide for Obesity Treatment and Diabetes Prevention.” New England Journal of Medicine, 2024. DOI: 10.1056/NEJMoa2410819. Summary: healio.com
- Aronne LJ, Horn DB, le Roux CW, et al. “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity” (SURMOUNT-5). New England Journal of Medicine, 2025;393(1):26–36. DOI: 10.1056/NEJMoa2416394. Summary: acc.org
- Managed Healthcare Executive – FDA approves Zepbound for obstructive sleep apnea in adults with obesity (December 2024): managedhealthcareexecutive.com
- Wikipedia – Tirzepatide (molecular structure, half-life, approval overview): en.wikipedia.org