Oral Tirzepatide for Type 2 Diabetes
There is currently no oral formulation of tirzepatide approved or available for clinical use—tirzepatide is administered exclusively as a once-weekly subcutaneous injection. 1
Available Formulation and Administration
Tirzepatide (Mounjaro®) is only available as a subcutaneous injection, not as an oral medication. 1, 2 The drug comes in single-dose prefilled pens or single-dose vials for subcutaneous administration. 1, 2
Approved Dosing Regimen
- Starting dose: 2.5 mg subcutaneously once weekly 1
- After 4 weeks: Increase to 5 mg subcutaneously once weekly 1
- Dose escalation: If additional glycemic control is needed, increase in 2.5 mg increments after at least 4 weeks on the current dose 1
- Maximum dose: 15 mg subcutaneously once weekly 1
- Administration timing: Once weekly at any time of day, with or without meals 1
- Injection sites: Abdomen, thigh, or upper arm, rotating sites with each dose 1
Clinical Indication
Tirzepatide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 1 It is a first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. 1, 3, 4
Efficacy Profile
Tirzepatide demonstrates unprecedented glycemic control and weight loss compared to other single agents for type 2 diabetes. 4, 5 In the SURPASS clinical trials:
- HbA1c reduction: 1.24% to 2.58% across doses 4
- Weight loss: 5.4 to 11.7 kg (mean weight change -8.47 kg compared to usual care) 6, 4
- Normoglycemia achievement: 23.0% to 62.4% of patients reached HbA1c <5.7% 4
- Significant weight loss: 20.7% to 68.4% of patients lost >10% of baseline body weight 4
Tirzepatide was superior to semaglutide 1 mg weekly for both glycemic control and weight loss. 6, 4, 2 It also outperformed dulaglutide 0.75 mg and titrated basal insulin. 2
Safety Considerations
Contraindications
- Personal or family history of medullary thyroid carcinoma 1
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
- Known serious hypersensitivity to tirzepatide or excipients 1
Key Warnings
Black Box Warning: Tirzepatide causes thyroid C-cell tumors in rats; human relevance is unknown. 1
Gastrointestinal adverse events are the most common, occurring in ≥5% of patients: nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain. 1, 2 These are typically mild to moderate and similar to GLP-1 receptor agonists. 4, 2
Pulmonary aspiration risk: Patients should inform healthcare providers of planned surgeries or procedures, as GLP-1 receptor agonists delay gastric emptying. 6, 1 For elective surgery, consider holding tirzepatide one week before the procedure. 6
Other Important Warnings
- Pancreatitis: Discontinue promptly if suspected 1
- Hypoglycemia: Risk increases when combined with insulin secretagogues or insulin; dose reduction of these agents may be necessary 1
- Acute kidney injury: Monitor renal function in patients with renal impairment experiencing severe gastrointestinal reactions 1
- Acute gallbladder disease: Has occurred in clinical trials 1
- Diabetic retinopathy: Monitor patients with history of diabetic retinopathy for progression 1
Clinical Positioning
Tirzepatide is recommended as a preferred option for patients with type 2 diabetes requiring high glucose-lowering effects with low hypoglycemia risk and weight loss. 6, 3
- For patients with established cardiovascular disease or chronic kidney disease: GLP-1 receptor agonists (including tirzepatide) with proven cardiovascular benefit are recommended alongside SGLT2 inhibitors 6
- For patients needing injectable therapy: GLP-1 receptor agonists are preferred over insulin due to lower hypoglycemia risk and weight loss benefits 6
- Tirzepatide probably reduces severe hypoglycemia compared with insulin (RR 0.21, moderate certainty of evidence) 6