See also: Overview of GLP-1 agonists
First, I'll introduce the original brand of tirzepatide, MOUNJARO.
Tirzepatide (Mounjaro)
Pronounced: tir ZEP a tide / mown JAHR OH
Mechanism: dual GLP-1/GIP receptor agonist
FDA-approved for: Type 2 diabetes
Mnemonic: “Tear zeppelin (over) Mount (Kiliman)jaro”
Tirzepatide is the first “twincretin” for type 2 diabetes. It is a GLP-1 agonist like the other medications in this chapter, and also a glucose-dependent insulinotropic polypeptide (GIP) agonist. GIP is similar to GLP-1. Both are secreted in the gut in response to food.
Tirzepatide (when added to metformin) can reduce A1c by up to 2.3%, which is superior to similar medications.
Tirzepatide is now approved for weight loss!
Tirzepatide (ZEPBOUND)
FDA-approved for: Type 2 diabetes
Mnemonic: “Zeppelin bound”
FDA-approved for: Chronic weight management
Zepbound is the formulation of tirzepatide FDA-approved for weight loss (November 2023) as an adjunct to diet and exercise. It is indicated for those with BMI of 30+ (obesity) or 27+ (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). It is the most effective weight loss medication available.
Tirzepatide (Mounjaro or Zepbound) is injected subcutaneously on a weekly basis.
Tirzepatide can lead to weight loss of up to 25 pounds over 10 months in patients with diabetes.
Over 72 weeks patients without diabetes lost 15%, 19%, and 21% of body weight on the 5, 10, and 15 mg weekly SQ injections, respectively. About 90% of those who received the 10- or 15-mg dose achieved ≥5% weight loss.
The most common side effects are nausea (~15%), diarrhea (~15%), and other gastrointestinal complaints.
Pharmacokinetic interactions
Cautions applicable to other GLP-1 agonists apply to tirzepatide. Serious hypersensitivity reactions such as anaphylaxis and angioedema have occurred with these drugs. It is contraindicated for use in patients with a personal or family history of medullary thyroid carcinoma and in those with multiple endocrine neoplasia type 2.
Dosing is essentially the same as with Mounjaro. Start 2.5 mg weekly injections subcutaneously. After 4 weeks, increase to 5 mg weekly. May increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The recommended maintenance dosages are 5 mg, 10 mg, or 15 mg weekly. Inject subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites.
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