What is Mounjaro (Tirzepatide)?
Mounjaro (tirzepatide) is a first-in-class dual incretin agonist that simultaneously activates both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, approved for improving glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise. 1, 2
Mechanism of Action
Tirzepatide is a synthetic peptide analog that combines dual receptor agonism through a novel "twincretin" approach 3:
- GIP receptor activation: Stimulates insulin secretion, decreases glucagon secretion, and plays a role in nutrient and energy metabolism 2
- GLP-1 receptor activation: Stimulates insulin secretion, decreases glucagon secretion, delays gastric emptying, suppresses appetite, and improves satiety 2
- Albumin binding: Contains a C20 fatty-diacid portion that binds to albumin via acylation technology, enabling once-weekly dosing with a half-life of approximately 5 days 3
Formulation and Administration
Tirzepatide is available as single-dose prefilled pens and single-dose vials for once-weekly subcutaneous injection. 1
- Dosing schedule:
- Initial: Not specified in provided evidence, but administered once weekly
- Taken with food in combination with other anti-diabetic medications when used as add-on therapy 1
Clinical Efficacy
In the phase III SURPASS trials, tirzepatide demonstrated superior outcomes compared to existing therapies 1:
- Glycemic control: Superior to dulaglutide 0.75 mg, semaglutide 1 mg, and both basal and prandial insulin 1
- Weight loss: Achieved reductions exceeding 20% of body weight, superior to comparator GLP-1 receptor agonists 1, 3
- Lipid metabolism: Demonstrated improvements in lipid profiles 3
- Insulin sensitivity: Significantly improved insulin sensitivity 3
Safety Profile
Tirzepatide has a safety profile consistent with GLP-1 receptor agonists 1:
- Common adverse events (mostly mild to moderate): Nausea, diarrhea, decreased appetite, and vomiting 1
- Hypoglycemia risk: Low risk of clinically significant or severe hypoglycemia 1
- Cardiovascular safety: No increased risk of major adverse cardiovascular events 1
Regulatory Status
- First approval: May 2022 in the United States under the brand name Mounjaro 2, 3
- Current approvals: USA, EU, Japan, and other countries 1
- Indication: Approved to improve glycemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise 1, 2
Development Pipeline
Tirzepatide is currently in development for additional indications 2:
- Phase III: Heart failure, obesity, and cardiovascular disorders in type 2 diabetes 2
- Phase II: Non-alcoholic steatohepatitis 2
- Under investigation for: Obstructive sleep apnea and reducing mortality/morbidity in obesity 2
Clinical Context
Tirzepatide represents a valuable addition to type 2 diabetes treatment options, particularly for patients requiring both improved glycemic control and significant weight reduction. 1 The dual incretin agonism provides a novel therapeutic approach that addresses multiple pathophysiologic mechanisms simultaneously, making it especially useful when GLP-1 receptor agonist monotherapy or traditional therapies have been inadequate 4, 5.