Clinical Overview: Tirzepatide for Improved Glycemic Control in Type 2 Diabetes

Tirzepatide (Mounjaro) is a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist used for improved glycemic control in type 2 diabetes, in addition to diet and exercise. The FDA approved tirzepatide for the treatment of type 2 diabetes on May 13, 2022.

Tirzepatide was evaluated in 5 different clinical trials (SURPASS-1, SURPASS-2, SURPASS-3, SURPASS-4, and SURPASS-5) at varying doses (5 mg, 10 mg, and 15 mg), as a stand-alone therapy or as an add-on to other diabetes treatments.² Patients randomized to receive the maximum recommended dose (15 mg) of tirzepatide as a standalone therapy experienced a lowering of their hemoglobin A1C level by ~1.6% compared to placebo.

When tirzepatide 15 mg was added to a long-acting insulin analog, a decrease of HbA1C level by ~ 1.5 % compared to placebo was seen.¹ The efficacy of tirzepatide was evaluated with other diabetes medications, including semaglutide, insulin degludec, and insulin glargine.

Patients who received 15 mg tirzepatide lowered their HbA1c by 0.5% compared to patients receiving semaglutide, 0.9% more than patients receiving insulin degludec, and 1% more than patients receiving insulin glargine.¹

Tirzepatide also showed a significant impact on weight loss in study participants. Patients who received 15 mg tirzepatide lost an average of 15 lbs more compared to placebo.

When insulin was used as an add-on in both arms, patients receiving 15 mg lost 23 lbs more than placebo. Patients receiving the maximum dose of tirzepatide lost an average of 12 lbs more than semaglutide, 29 pounds more than insulin degludec, and 27 pounds more than insulin glargine.¹

Mechanisms of Action^1,2

Tirzepatide is a dual-acting agonist on the GIP and GLP-1 receptors, resulting in improved glycemic control as an adjunct to diet and exercise.

Dosage and Administration²

• Tirzepatide is available as a subcutaneous injection in strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg per 0.5 ml in a single-dose pen.
• Administer as a subcutaneous injection once weekly, with or without food.
• Tirzepatide may be administered to the abdomen, thigh, or upper arm. Rotate injection sites with each dose.
• Recommended starting dose is 2.5 mg injected subcutaneously once weekly. After 4 weeks, titrate dose to 5 mg injected subcutaneously once weekly.
• If additional glucose control is needed, dose may be increased by 2.5 mg every 4 weeks, with a maximum dose of 15 mg subcutaneously once a week.
• Tirzepatide delays gastric emptying and may impact the absorption of concomitantly administered oral medication. Consider spacing oral medications from when tirzepatide is administered.

Contraindications²

Tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid cancer (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Tirzepatide is contraindicated in patients with known hypersensitivity to tirzepatide or any of its excipients.

Adverse Events (AEs)^1,2

The most commonly reported AEs with tirzepatide are nausea, vomiting, diarrhea, constipation, decreased appetite, abdominal pain, and dyspepsia.

Warnings and Precautions²

Tirzepatide is known to cause thyroid C-cell tumors in rats. The relevance of this finding to humans is unknown. Pharmacists should counsel patients about the potential risk of MTC, advise on the symptoms of a thyroid tumor, and recommend follow-up with their health care provider if a tumor is suspected.

Tirzepatide has not been studied in patients with severe gastrointestinal disease and is not recommended for this patient population.

Pancreatitis has been reported in studies. Pharmacists should counsel patients on the symptoms of pancreatitis and advise them to discontinue use if suspected.

Concomitant use of insulin and insulin secretagogues may result in hypoglycemia. Educate patients on the signs and symptoms of hypoglycemia. Consider a dose reduction of insulin or insulin secretagogue, as necessary.

Tirzepatide may reduce the efficacy of oral contraceptives due to delayed gastric emptying.Patients on oral contraceptives should be advised to switch to a non-oral contraceptive or add on a barrier contraceptive method for 4 weeks after initiating tirzepatide and 4 weeks after every dose escalation.

Gastrointestinal adverse effects of tirzepatide, such as vomiting and diarrhea, can lead to dehydration. If severe, this may result in acute kidney injury. Pharmacists should advise patients with renal impairment of this potential risk.

Rapid glucose control is associated with a temporary worsening of diabetic retinopathy in patients. Pharmacists should counsel patients with a history of diabetic retinopathy of this phenomenon and encourage them to consult their physician if they notice any changes in their vision.

Acute gallbladder disease has been reported in clinical trials. Patients should be counseled on the signs of gallbladder disease and advised to follow up with their health care provider if suspected.

Pregnancy and Lactation²

Limited data are available for the use of tirzepatide in pregnancy. Some animal studies suggest a potential risk of fetal harm. Tirzepatide should only be used during pregnancy if the potential benefit outweighs the risk of harm.

No data are currently available for use during lactation.

References

1. FDA Approves novel, dual-targeted treatment for Type 2 Diabetes. Accessed June 7, 2022

2. Mounjaro Prescribing Information. Lilly USA LLC. May 2022. Accessed June 7, 2022