Tirzepatide injection for subcutaneous use is available in the United States with two different brand names—Mounjaro™ and Zepbound™—that have different FDA indications. On this page, we will discuss tirzepatide from the viewpoint of its use for chronic weight management in adults. (The exact same medication is also available under the brand name Mounjaro™ with an FDA indication “as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus”.)
On this page, we will provide basic prescribing information about this medication. Links to other articles on this website with more advanced information and tips related to this medication and/or related topics are provided below—under Related Pages
FDA indications
According to the Prescribing Information, tirzepatide (Zepbound™) has been approved by the United States Food and Drug Administration (emphasis in red added by us):
“…as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of:
– 30 kg/m2 or greater (obesity) or
– 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease).”
Mechanism of action/ Pharmacodynamics
Tirzepatide has two mechanisms of action, both related to hormones that are secreted in the intestine and are involved in the regulation of appetite, satiety, and caloric intake. They are:
1. Glucagon-like peptide-1 (GLP-1), and
2. Glucose-dependent insulinotropic polypeptide (GIP).
GLP-1 is well-established as regulating appetite and caloric intake. GIP may also help regulate food intake and glucose metabolism when given in combination with a GLP-1 receptor agonist (de Mesquita et al., 2023).
Tirzepatide is BOTH of the following:
1. GLP-1 receptor agonist
2. GIP receptor agonist
Treatment with tirzepatide is associated with the following effects (Wadden et al., 2023; Prescribing Information):
1. Effects on caloric intake and body weight
– Decreased calorie intake due to increased satiety and decreased appetite
– Decreased body weight, with more fat loss than lean mass loss)
2. Effects on glucose metabolism
– Increased insulin secretion in a glucose-dependent manner
– Decreased glucagon secretion
– Increased insulin sensitivity
– Possible decrease in blood glucose due to the above-mentioned effects.
I think that can organize potential harms from any medication in decreasing order of seriousness as follows:
- Contraindications (don’t even give the medication)
- Boxed warning (if the medication can be given, this is the highest level of warning)
- Warnings and Precautions
- Adverse reactions
Contraindications
1. Personal or family history of medullary thyroid carcinoma
2. Multiple Endocrine Neoplasia type 2 (MEN type 2).
Boxed warning
The boxed warning (often wrongly called a “black box warning”) shown in the image below notes that tirzepatide causes thyroid C-cell tumors in rats.
This is the reason for the contraindications in the previous section.
Warnings and Precautions
-
- Severe gastrointestinal disease
- Acute kidney injury
- Acute gallbladder disease
- Acute pancreatitis
- Hypersensitivity reactions
- Hypoglycemia
- Diabetic retinopathy
- Suicidal behavior and ideation
- Severe gastrointestinal disease
Adverse reactions
In clinical trials, the term “adverse events” refers to any undesirable symptoms/ signs that either started or got worse during the clinical trial whether or not they were related to the study drug. So, how do we know whether an adverse event was or was caused by the study drug? There is no foolproof way to determine this.
On this website, we consider an adverse event to tentatively be a “side effect” of the drug if it was reported in participants who received the study drug at least twice as often as in those who received placebo.
Adverse events that occurred in tirzepatide clinical trials and met the following two criteria are listed below (Prescribing Information):
1. Occurred in patients who received tirzepatide injection at least twice as often as in those who received placebo
2. Occurred in patients who received tirzepatide injection at least 2% more often than in those who received placebo (that is, with a drug-placebo difference of 2% or more).
1. Gastrointestinal symptoms: nausea (20%), diarrhea (15%), vomiting (11%), constipation (6%), dyspepsia (6%), abdominal pain (5%), eructation (4%), gastroesophageal reflux disease (3%), abdominal distension (2%) and flatulence (2%).
2. Injection site reactions (6%),
3. Fatigue (4%),
4. Hair loss (4%)
5. Dizziness (2%)
6. Hypotension (2%).
Dosing
Tirzepatide is available as a single-dose prefilled pen for subcutaneous injection. Patient may self-administer or ask help from another person when administering in the stomach or thigh. If injecting into back of the upper arm, patient may seek help from another person.
Start with 2.5 mg injection, once weekly.
Increase to 5 mg, once weekly, after 4 weeks
Increase by 2.5 mg once weekly, once the patient has been on the current dose for 4 weeks.
Maintenance dose: 5 mg, 10 mg, or 15 mg once weekly, depending on treatment response and tolerability
Maximum dose: 15 mg subcutaneously once weekly
Instruct patient to rotate injection site with each dose.
Dosage forms and strengths
Tirzepatide is available as a single-use, prefilled syringe in 6 different strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
Important! This page does not provide all the information needed to prescribe this medication. Please refer to the full Prescribing Information (see the link below) before prescribing this medication.
Related Pages
GLP-1 agonists
A simple primer on what GLP-1 agonists are
Semaglutide injection (Wegovy™) for weight loss in obesity and overweight
Semaglutide injection (Wegovy™): Side effects
Semaglutide injection (Wegovy™): Serious side effects, warnings, and contraindications
Semaglutide injection (Wegovy™): Basic information
Tirzepatide (Zepbound™): Basic information
Metabolic side effects: General
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References
de Mesquita YLL, Pera Calvi I, Reis Marques I, Almeida Cruz S, Padrao EMH, Carvalho PEP, da Silva CHA, Cardoso R, Moura FA, Rafalskiy VV. Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials. Int J Obes (Lond). 2023 Oct;47(10):883-892. doi: 10.1038/s41366-023-01337-x. Epub 2023 Jul 17. PMID: 37460681.
Tan B, Pan XH, Chew HSJ, Goh RSJ, Lin C, Anand VV, Lee ECZ, Chan KE, Kong G, Ong CEY, Chung HC, Young DY, Chan MY, Khoo CM, Mehta A, Muthiah MD, Noureddin M, Ng CH, Chew NWS, Chin YH. Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Int J Obes (Lond). 2023 Aug;47(8):677-685. doi: 10.1038/s41366-023-01321-5. Epub 2023 May 31. PMID: 37253796.
Tirzepatide (Zepbound™) Prescribing Information. Available at https://pi.lilly.com/us/zepbound-uspi.pdf. Last accessed on December 8, 2023.
Wadden TA, Chao AM, Moore M, Tronieri JS, Gilden A, Amaro A, Leonard S, Jakicic JM. The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities. Curr Obes Rep. 2023 Dec 2. doi: 10.1007/s13679-023-00534-z. Epub ahead of print. PMID: 38041774.
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