Am Fam Physician. 2024;110(2):199-200
Author disclosure: No relevant financial relationships.
Tirzepatide (Zepbound), also known as Mounjaro when used for the treatment of diabetes mellitus, acts on the glucagon-like peptide-1 (GLP-1) receptor and the gastric inhibitory polypeptide to regulate appetite and food intake. Zepbound is labeled as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a body mass index (BMI) greater than 30 kg per m2, or a BMI greater than 27 kg per m2 and at least one weight-related comorbidity (e.g., hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease).1
| Drug | Dosage | Dose form | Cost of full course* |
|---|---|---|---|
| Tirzepatide (Zepbound) | Initial dosage: 2.5 mg weekly Titrate by 2.5 mg every 4 weeks to a target dosage of 5 mg to 15 mg (maximum dosage) weekly | Single-use autoinjection pen: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL | $1,000 |
SAFETY
Hypoglycemia will occur in about 4% of patients with type 2 diabetes but is rare (less than 0.5%) in those without diabetes.2 As with other GLP-1 receptor agonists, tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2, because the development of thyroid C-cell tumors has been shown in rats. Severe gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and abdominal pain, will occur in up to 3% of patients taking tirzepatide. Acute kidney injury occurred infrequently, according to post-marketing reports, and mostly in patients experiencing nausea, vomiting, diarrhea, or dehydration. Tirzepatide does not require adjustment for renal or hepatic disease. Patients taking tirzepatide do not appear to be at increased risk of gallbladder disease or pancreatitis. Tirzepatide delays gastric emptying, which theoretically can reduce the effectiveness of oral contraceptives. Patients should use a non–oral contraceptive method or add a barrier method for the first 4 weeks after initiation and following dose changes, which may take several months due to the long titration period of tirzepatide. It should not be used in pregnant patients and should be discontinued if pregnancy occurs. Tirzepatide has not been studied in patients who are breastfeeding. Based on experience with other weight-loss medications, tirzepatide carries the same warning of increased suicidal behavior and ideation. Patients should be monitored for symptom emergence. Tirzepatide should not be prescribed to patients with a history of suicidal attempts or active ideation. Only small proportions of patients in clinical trials have been older than 65 years. Tirzepatide has not been studied in children.
TOLERABILITY
As with other GLP-1 receptor agonists, nausea, vomiting, diarrhea, and abdominal pain are common, with 6.5% of patients discontinuing tirzepatide because of adverse effects (vs. 2.6% with placebo). For most patients, adverse effects are mild to moderate, resolve with continued use, and occur mostly during dose titration.
EFFECTIVENESS
Tirzepatide has been studied in a trial of 2,539 patients who had obesity but not diabetes, with a BMI of more than 30 kg per m2 or a BMI of more than 27 kg per m2 plus at least one weight-related comorbid condition.2 Based on these results, 90% of patients will lose at least the historically relevant 5% of body weight. More clinically significant weight-loss goals of 10%, 15%, and 20% will be achieved by 80%, 70%, and more than 50% of patients, respectively (57% of patients taking 15 mg of tirzepatide vs. 3% of patients given placebo will lose 20% of their body weight). Only two patients need to be treated with tirzepatide instead of placebo for one patient to lose 20% or more of their body weight. Improvements in cardiometabolic risk factors such as waist circumference and blood pressure also occurred. In patients with prediabetes at baseline, 95% reverted to normoglycemia after 72 weeks of treatment with tirzepatide, compared with 62% of patients receiving placebo. Tirzepatide has not been compared directly with other weight-loss medications. The effects of tirzepatide on prevention of diabetes, cardiovascular outcomes in patients without diabetes, and how much weight may be regained when treatment is discontinued are unknown.
PRICE
Tirzepatide costs approximately $1,000 per month. This is slightly less expensive than other drugs in this class labeled for obesity, such as liraglutide (Saxenda) and semaglutide (Wegovy), which cost about $1,300. Tirzepatide is often covered by commercial insurance formularies. Some state Medicaid plans may cover it, and Medicare may consider it for select patients once its cardiovascular benefits have been established.
SIMPLICITY
Tirzepatide is formulated as a three-step autoinjector, which offers ease of administration. The dosage is titrated every 4 weeks to a maintenance level of 5 mg, 10 mg, or 15 mg weekly, depending on treatment response and tolerance.
BOTTOM LINE
Tirzepatide is highly effective and may be considered for patients desiring significant weight loss who are able to administer weekly subcutaneous injections. When no contraindications exist, tirzepatide is easy to prescribe, administer, and tolerate. However, long-term effectiveness has not been demonstrated. Other treatments with proven benefits to affect cardiovascular outcomes and mortality should be used in patients with cardiovascular disease.
