Tirzepatide: how it works, trial results, uses and side effects
Clinical review pending
How tirzepatide affects blood sugar and body weight, what studies show about diabetes and sleep apnoea, and the side effects and limits to consider.
Tirzepatide can lower blood sugar in people with type 2 diabetes and bring about substantial weight loss in people with obesity. It activates the receptors of two gut hormones and, among other effects, reduces hunger. How much blood sugar and weight fall depends on the dose and the population studied. Digestive symptoms are common; less frequent but serious risks also need to be considered.
What is tirzepatide?
Tirzepatide is a synthetic peptide made up of 39 amino acids. It activates receptors for GIP and GLP-1, two hormones released by the gut after eating. This makes it a dual GIP and GLP-1 receptor agonist. Other medicines in this area act only on the GLP-1 receptor. 1
Eli Lilly markets tirzepatide under two brand names: Mounjaro for type 2 diabetes, and Zepbound for weight management and obstructive sleep apnoea. In sleep apnoea, the upper airway repeatedly narrows or closes during sleep, interrupting breathing. Both products are injected under the skin once a week, a route called subcutaneous injection. The brand names and indications described here refer to the United States. 1
How does tirzepatide work?
Through the GIP and GLP-1 receptors, tirzepatide stimulates the pancreas to release insulin when blood sugar is elevated. It also reduces the release of glucagon, a hormone that raises blood sugar. Tirzepatide slows stomach emptying and acts on the centres that regulate appetite. Hunger and food intake decrease. Together, these effects help lower blood sugar and reduce how much a person eats. 1
The SURMOUNT-1 obesity trial illustrates how much weight can change: over 72 weeks, adults without diabetes lost an average of 15.0% to 20.9% of their body weight across three dose groups. The placebo group lost 3.1%. 2 Trials in type 2 diabetes also found substantial reductions in body weight and HbA1c, a measure of longer-term blood sugar levels. 1
Is tirzepatide approved by the FDA?
The US Food and Drug Administration has approved tirzepatide for several uses. However, the approval status of two of the five uses listed here remains unresolved in this draft: treatment in children and reduction of cardiovascular risk.
| Date | Brand | Approval |
|---|---|---|
| 2022 | Mounjaro | Initial approval for type 2 diabetes. 1 |
| 2023 | Zepbound | Approval for long-term weight management. 3 |
| December 2024 | Zepbound | First approved medicine for obstructive sleep apnoea in adults with obesity. 4 |
| December 2025 | Mounjaro | Extension to children aged 10 and over: approval claim not yet confirmed. |
| August 2026 | Mounjaro | Reduction of major cardiovascular events in adults with type 2 diabetes at high risk: approval claim not yet confirmed. |
What is tirzepatide prescribed for?
Mounjaro is used alongside diet and physical activity to improve blood sugar control in type 2 diabetes. This is an approved US use in adults. The statements about treatment in children aged 10 and over and reduction of major cardiovascular events in adults with type 2 diabetes at high risk have not yet been confirmed as US approvals in this draft.
In the United States, Zepbound is approved for weight management in adults with obesity, defined here as a body mass index (BMI) of 30 or more. For adults with overweight, the threshold is a BMI of at least 27 together with at least one weight-related condition, such as high blood pressure or high cholesterol. Zepbound is also approved to treat moderate to severe obstructive sleep apnoea in adults with obesity. 3
Tirzepatide must not be used by someone with a personal or family history of medullary thyroid carcinoma. Multiple endocrine neoplasia type 2 and a known allergy to tirzepatide also rule out its use. 1
What are the side effects?
Digestive symptoms are the most common side effects of tirzepatide. They are usually most pronounced when the dose is increased. Reported side effects include:
- Nausea
- Diarrhoea
- Vomiting
- Constipation
- Abdominal pain
- Reduced appetite
- Indigestion
- Fatigue
- Injection-site reactions
- Allergic reactions
- Belching
- Hair loss
- Heartburn
Less common but more serious risks include:
- Thyroid C-cell tumours: the US prescribing information carries a prominent “boxed warning”. It is based on studies in rodents. Whether tirzepatide causes these tumours in humans is not known. 1
- Pancreatitis, or inflammation of the pancreas
- Gallbladder disease, including gallstones
- Acute kidney injury, usually associated with dehydration from vomiting or diarrhoea
- Worsening of diabetic retinopathy, a form of damage to the retina, in people with type 2 diabetes
- Low blood sugar, particularly when taken alongside insulin or a sulfonylurea
- Delayed stomach emptying: during surgery or anaesthesia, this can increase the risk of stomach contents entering the airway, known as aspiration
Frequently asked questions
How does tirzepatide differ from GLP-1 agonists?
Tirzepatide activates both GIP and GLP-1 receptors, affecting appetite, stomach emptying and insulin release. This two-receptor approach explains the term “dual agonist”. Semaglutide acts only on the GLP-1 receptor. Tirzepatide is the first member of its drug class; research has also shown reductions in LDL cholesterol and triglycerides. 5
A network meta-analysis assessed 28 randomised controlled trials involving 23,622 adults with type 2 diabetes. This kind of analysis compares treatments across multiple studies. Compared with placebo, HbA1c fell by 1.96 percentage points with 15 mg tirzepatide and by 1.59 percentage points with 2.0 mg semaglutide. The analysis judged these blood sugar effects to be comparable. Weight loss relative to placebo was 9.57 kg with tirzepatide and 4.97 kg with semaglutide. These findings come from a network of studies, not a direct comparison of all participants within a single trial. 6
What did SURMOUNT-1 find about weight loss?
In SURMOUNT-1, adults without type 2 diabetes lost an average of 15.0% to 20.9% of their body weight over 72 weeks, depending on the dose group. The placebo group lost 3.1%. The study enrolled 2,539 adults with either obesity or overweight and at least one weight-related complication. These averages describe the results for each group; weight loss varied between individuals. 2
SURMOUNT-4 examined what happened to weight when treatment continued and when participants switched to placebo. First, participants received tirzepatide during a 36-week open-label lead-in period. “Open-label” means that the treatment was known. During this period, they lost an average of 20.9% of their body weight. Researchers then randomly assigned 670 people either to continue tirzepatide or to switch to placebo.
Weight fell by a further 5.5% with continued tirzepatide. After switching to placebo, it increased by 14.0%. The study reported a difference of 19.4 percentage points. From the start of the study, total weight loss was 25.3% with continued treatment and 9.9% after switching to placebo. 7
Does tirzepatide work in people with type 2 diabetes and obesity?
Yes. A trial in adults with type 2 diabetes and obesity also found substantial weight loss. SURMOUNT-2 followed 938 adults for 72 weeks. Average weight loss was 12.8% with 10 mg tirzepatide, 14.7% with 15 mg and 3.2% with placebo. The study reported treatment differences versus placebo of 9.6 and 11.6 percentage points, respectively. 8
Average weight loss was lower than in SURMOUNT-1, which enrolled people without diabetes. These are results from two different trials.
What is tirzepatide’s FDA approval status?
Tirzepatide is approved in the United States under the brand names Mounjaro and Zepbound. Of the five uses listed in this draft, two approval claims remain unconfirmed. Mounjaro received US approval for type 2 diabetes in May 2022. [9] The later extensions to children and adolescents aged 10 and over [10] and to cardiovascular risk reduction in adults with type 2 diabetes at high risk [11] remain unresolved here.
Zepbound received approval in November 2023 [12] for long-term weight management in adults with obesity or overweight and at least one weight-related condition. Approval for moderate to severe obstructive sleep apnoea in adults with obesity followed in December 2024.
Custom-prepared formulations are known in the United States as “compounded tirzepatide”. They are not FDA-approved and have not been assessed by the agency for safety, effectiveness or quality. 13
What does research show about tirzepatide and sleep apnoea?
The SURMOUNT-OSA trials studied adults with moderate to severe obstructive sleep apnoea and obesity. In people who were not receiving positive airway pressure (PAP) therapy, the apnoea–hypopnoea index fell by 25.3 events per hour at the maximum tolerated tirzepatide dose. This index counts breathing interruptions and episodes of reduced airflow; a lower score means fewer such events. 14
The trial lasted 52 weeks and was one of two studies involving a total of 469 participants. Tirzepatide reduced the index by 20.0 more events per hour than placebo. The 95% confidence interval, which describes the statistical uncertainty around the estimate, ranged from 14.2 to 25.8 events per hour. The benefit was associated with weight loss. These results supported FDA approval for this use in December 2024. 14
Can tirzepatide reduce the risk of developing type 2 diabetes?
In an analysis of SURMOUNT-1, adults with obesity and prediabetes developed type 2 diabetes much less often with tirzepatide than with placebo. The analysis covered 1,032 participants over 176 weeks. Type 2 diabetes developed in 1.3% of the tirzepatide group and 13.3% of the placebo group. The reported hazard ratio was 0.07, a measure comparing how often new cases developed in the two groups over time. 15
Over the same period, average weight loss was 12.3% with 5 mg tirzepatide, 18.7% with 10 mg and 19.7% with 15 mg. The placebo group lost 1.3%. These findings apply to the population studied—adults with obesity and prediabetes—during the 176-week period. 15
How does weight loss compare with semaglutide?
Comparative research points to greater weight loss with tirzepatide than with semaglutide. How informative that comparison is depends on the doses and study design. Both medicines increase digestive side effects, which deserve particular attention at higher tirzepatide doses.
A 2025 meta-analysis combined seven comparative studies involving 28,980 participants. Five were observational studies and two were randomised trials. The odds of losing at least 10% of body weight were statistically significantly higher with tirzepatide, although the results varied substantially across studies. 16
A 2024 network meta-analysis included 28 randomised controlled trials with 23,622 adults with type 2 diabetes. Relative to placebo, body weight fell by 9.57 kg with 15 mg tirzepatide and by 4.97 kg with 2.0 mg semaglutide. These figures come from a comparison across multiple studies and should not be read as the results of a single head-to-head trial. 6
Sources
- Sources: FDA prescribing information for Mounjaro and Zepbound (tirzepatide); the SURMOUNT-1 obesity trial in the New England Journal of Medicine (Jastreboff et al., 2022, DOI: 10.1056/NEJMoa2206038), indexed on PubMed; and the FDA approval announcement for obstructive sleep apnoea. This document is educational and does not constitute medical advice. Original reference