Tirzepatide is a once-weekly subcutaneous injection to treat type 2 diabetes in conjunction with diet and exercise.
On May 13, 2022, the FDA approved tirzepatide (Mounjaro) for the treatment of type 2 diabetes (T2D) in conjunction with diet and exercise.1 Tirzepatide has a dual mechanism of action as an agonist to glucose-dependent insulinotropic polypeptide (GIP) receptors and to glucagon-like peptide-1 (GLP-1) receptors. As such, tirzepatide acts to modulate insulin and glucagon release, which can improve blood glucose control.2
Tirzepatide efficacy was demonstrated in a series of trials (SURPASS-1 through SURPASS-5) aimed at improving glycemic control in participants with T2D in addition to diet and exercise. SURPASS-1 (NCT03954834) compared tirzepatide monotherapy to placebo, while SURPASS-2 through SURPASS-5 allowed participants to use additional background therapy.
SURPASS-2 (NCT03987919) compared tirzepatide with semaglutide in addition to metformin. Participants were allowed to use metformin or metformin plus a sodium/glucose cotransporter 2 inhibitor (SGLT2I); SURPASS-3 (NCT03882970) compared tirzepatide with long-acting insulin degludec; SURPASS-4 (NCT03730662) compared tirzepatide to long-acting insulin glargine in participants concomitantly taking a background therapy regimen of up to 3 of the following medications: metformin, an SGLT2I, and/or a sulfonylurea; and SURPASS-5 (NCT04039503) evaluated patients who administered insulin glargine with or without metformin who were randomly assigned to tirzepatide or placebo.
The trials included a total of 5870 participants and studied tirzepatide 5-mg, 10-mg, and 15-mg doses for a duration of either 40 or 52 weeks.
Gastrointestinal adverse events (AEs) were most common with tirzepatide and included nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain. These AEs were more common during dose escalation but tended to decrease with time. Concomitant use of sulfonylureas or insulin can increase the risk of hypoglycemia.
Tirzepatide carries a boxed warning. In rats, tirzepatide causes thyroid C-cell tumors in a dose- and duration-dependent exposure. The risk of thyroid tumors in humans is currently not known, but tirzepatide it is contraindicated in patients with a family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2. All patients should be informed of the potential risk for MTC and of the presenting symptoms of such tumors in order to self-monitor.
Pancreatitis and acute gallbladder disease are associated with use of GLP-1 receptor agonists. Tirzepatide has not been studied in patients with a history of pancreatitis and the effect on lactation or infant exposure is unknown. Patients using oral contraceptives should switch to or add a nonoral contraceptive method for 4 weeks after initiation and after each dose escalation because of the resultant delay in gastric emptying. Tirzepatide is not indicated for use in patients with type 1 diabetes.
The approved starting dosage of tirzepatide is 2.5 mg once weekly as a subcutaneous injection to the abdomen, thigh, or upper arm. Injection sites should be rotated weekly. As needed for glycemic control, the dosage may be increased by 2.5 mg every 4 weeks, with a maximum dose of 15 mg injected subcutaneously weekly Tirzepatide may be administered without regard to meals. Tirzepatide is supplied as a package of 4 prefilled, single-dose pens. The medication can be stored in the refrigerator but is stable at room temperature for up to 21 days.