Get your patient on Mounjaro (Tirzepatide)

• The recommended starting dosage is 2.5 mg injected subcutaneously once weekly. (
  2.1 Dosage

  • The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]
    . The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control.
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly.
  • If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage of MOUNJARO is:
    • 15 mg injected subcutaneously once weekly in adults.
    • 10 mg injected subcutaneously once weekly in pediatric patients.
  • If a dose is missed, instruct patients to administer MOUNJARO as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
  • The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
  )
• After 4 weeks, increase to 5 mg injected subcutaneously once weekly. (
  2.1 Dosage

  • The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]
    . The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control.
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly.
  • If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage of MOUNJARO is:
    • 15 mg injected subcutaneously once weekly in adults.
    • 10 mg injected subcutaneously once weekly in pediatric patients.
  • If a dose is missed, instruct patients to administer MOUNJARO as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
  • The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
  )
• If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. (
  2.1 Dosage

  • The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]
    . The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control.
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly.
  • If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage of MOUNJARO is:
    • 15 mg injected subcutaneously once weekly in adults.
    • 10 mg injected subcutaneously once weekly in pediatric patients.
  • If a dose is missed, instruct patients to administer MOUNJARO as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
  • The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
  )
• Maximum dosage (
  2.1 Dosage

  • The recommended starting dosage of MOUNJARO is 2.5 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions
    [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)]
    . The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control.
  • After 4 weeks, increase the dosage to 5 mg injected subcutaneously once weekly.
  • If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage of MOUNJARO is:
    • 15 mg injected subcutaneously once weekly in adults.
    • 10 mg injected subcutaneously once weekly in pediatric patients.
  • If a dose is missed, instruct patients to administer MOUNJARO as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
  • The day of weekly administration can be changed, if necessary, as long as the time between the two doses is at least 3 days (72 hours).
  ):
  
  • Adults: 15 mg subcutaneously once weekly.
  • Pediatric patients 10 years of age and older: 10 mg subcutaneously once weekly.
• Administer once weekly at any time of day, with or without meals. (
  2.2 Important Administration Instructions

  • Prior to initiation, train patients and their caregiver(s) on proper injection technique
    [see Instructions for Use]
    . A patient may self-inject if a healthcare provider determines that it is appropriate.
  • Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).
  • Administer MOUNJARO once weekly, any time of day, with or without meals.
  • Inject MOUNJARO subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm.
  • Rotate injection sites with each dose.
  • Inspect MOUNJARO visually before use. It should appear clear and colorless to slightly yellow. Do not use MOUNJARO if particulate matter or discoloration is seen.
  • When using MOUNJARO with insulin, administer as separate injections and never mix. It is acceptable to inject MOUNJARO and insulin in the same body region, but the injections should not be adjacent to each other.
  )
• Inject subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm. (
  2.2 Important Administration Instructions

  • Prior to initiation, train patients and their caregiver(s) on proper injection technique
    [see Instructions for Use]
    . A patient may self-inject if a healthcare provider determines that it is appropriate.
  • Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).
  • Administer MOUNJARO once weekly, any time of day, with or without meals.
  • Inject MOUNJARO subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm.
  • Rotate injection sites with each dose.
  • Inspect MOUNJARO visually before use. It should appear clear and colorless to slightly yellow. Do not use MOUNJARO if particulate matter or discoloration is seen.
  • When using MOUNJARO with insulin, administer as separate injections and never mix. It is acceptable to inject MOUNJARO and insulin in the same body region, but the injections should not be adjacent to each other.
  )
• Rotate injection sites with each dose. (
  2.2 Important Administration Instructions

  • Prior to initiation, train patients and their caregiver(s) on proper injection technique
    [see Instructions for Use]
    . A patient may self-inject if a healthcare provider determines that it is appropriate.
  • Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).
  • Administer MOUNJARO once weekly, any time of day, with or without meals.
  • Inject MOUNJARO subcutaneously in the abdomen, thigh, or another person should inject in the back of the upper arm.
  • Rotate injection sites with each dose.
  • Inspect MOUNJARO visually before use. It should appear clear and colorless to slightly yellow. Do not use MOUNJARO if particulate matter or discoloration is seen.
  • When using MOUNJARO with insulin, administer as separate injections and never mix. It is acceptable to inject MOUNJARO and insulin in the same body region, but the injections should not be adjacent to each other.
  )

Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens or single-dose vials, each available in the following strengths:

• 2.5 mg/0.5 mL
• 5 mg/0.5 mL
• 7.5 mg/0.5 mL
• 10 mg/0.5 mL
• 12.5 mg/0.5 mL
• 15 mg/0.5 mL

• Pregnancy:
  Based on animal studies, may cause fetal harm. (
  8.1 Pregnancy

  Risk Summary

  Available data with MOUNJARO use in pregnant women are insufficient to evaluate for a drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy

  (see Clinical Considerations)

  . Based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide during pregnancy. MOUNJARO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

  In pregnant rats administered tirzepatide during organogenesis, fetal growth reductions and fetal abnormalities occurred at clinical exposure in maternal rats based on AUC. In rabbits administered tirzepatide during organogenesis, fetal growth reductions were observed at clinically relevant exposures based on AUC. These adverse embryo/fetal effects in animals coincided with pharmacological effects on maternal weight and food consumption

  (see Data)

  .

  The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7% and has been reported to be as high as 20–25% in women with an HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

  Clinical Considerations

  Disease-Associated Maternal and/or Embryo/Fetal Risk

  Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

  Data

  Animal Data

  In pregnant rats given twice weekly subcutaneous doses of 0.02, 0.1, and 0.5 mg/kg tirzepatide (0.03-, 0.07-, and 0.5-fold the MRHD of 15 mg once weekly based on AUC) during organogenesis, increased incidences of external, visceral, and skeletal malformations, increased incidences of visceral and skeletal developmental variations, and decreased fetal weights coincided with pharmacologically-mediated reductions in maternal body weights and food consumption at 0.5 mg/kg. In pregnant rabbits given once weekly subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg tirzepatide (0.01-, 0.06-, and 0.2-fold the MRHD) during organogenesis, pharmacologically-mediated effects on the gastrointestinal system resulting in maternal mortality or abortion in a few rabbits occurred at all dose levels. Reduced fetal weights associated with decreased maternal food consumption and body weights were observed at 0.1 mg/kg. In a pre- and post-natal study in rats administered subcutaneous doses of 0.02, 0.10, or 0.25 mg/kg tirzepatide twice weekly from implantation through lactation, F₁pups from F₀maternal rats given 0.25 mg/kg tirzepatide had statistically significant lower mean body weight when compared to controls from post-natal day 7 through post-natal day 126 for males and post-natal day 56 for females.
  )
• Females of Reproductive Potential:
  Advise females using oral contraceptives to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation. (
  8.3 Females and Males of Reproductive Potential

  Contraception

  Use of MOUNJARO may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying. This delay is largest after the first dose and diminishes over time. Advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation with MOUNJARO

  [see Drug Interactions (7.2) and Clinical Pharmacology (12.2,12.3)].
  )

MOUNJARO is contraindicated in patients with:

• A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  [see Warnings and Precautions (

  5.1 Risk of Thyroid C-Cell Tumors

  In both sexes of rats, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in a 2-year study at clinically relevant plasma exposures

  [see Nonclinical Toxicology (13.1)]

  . It is unknown whether MOUNJARO causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

  MOUNJARO is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of MOUNJARO and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

  Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with MOUNJARO. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  )]
  .
• Known serious hypersensitivity to tirzepatide or any of the excipients in MOUNJARO. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with MOUNJARO
  [see Warnings and Precautions (

  5.4 Hypersensitivity Reactions

  Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with MOUNJARO. If hypersensitivity reactions occur, discontinue use of MOUNJARO; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in MOUNJARO

  [see Contraindications (4), Adverse Reactions (6.2)]

  .

  Anaphylaxis and angioedema have been reported with GLP-1 receptor agonists. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with MOUNJARO.

  )]
  .

• Acute Pancreatitis:
  Has been observed in patients treated with GLP-1 receptor agonists, or MOUNJARO. Discontinue if pancreatitis is suspected. (
  5.2 Acute Pancreatitis

  Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or MOUNJARO

  [see Adverse Reactions (6)]

  .

  After initiation of MOUNJARO, observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue MOUNJARO and initiate appropriate management.
  )
• Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin:
  Concomitant use with an insulin secretagogue or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing dose of insulin secretagogue or insulin may be necessary. (
  5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

  Patients receiving MOUNJARO in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia

  [see Adverse Reactions (6.1), Drug Interactions (7.1)]

  .

  The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
  )
• Hypersensitivity Reactions:
  Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. Discontinue MOUNJARO if suspected and promptly seek medical advice. (
  5.4 Hypersensitivity Reactions

  Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with MOUNJARO. If hypersensitivity reactions occur, discontinue use of MOUNJARO; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in MOUNJARO

  [see Contraindications (4), Adverse Reactions (6.2)]

  .

  Anaphylaxis and angioedema have been reported with GLP-1 receptor agonists. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with MOUNJARO.
  )
• Acute Kidney Injury Due to Volume Depletion:
  Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. (
  5.5 Acute Kidney Injury Due to Volume Depletion

  There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or MOUNJARO. The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea

  [see Adverse Reactions (6)]

  .

  Monitor renal function in patients reporting adverse reactions to MOUNJARO that could lead to volume depletion, especially during dosage initiation and escalation of MOUNJARO.
  )
• Severe Gastrointestinal Adverse Reactions:
  Use has been associated with gastrointestinal adverse reactions, sometimes severe. MOUNJARO is not recommended in patients with severe gastroparesis. (
  5.6 Severe Gastrointestinal Adverse Reactions

  Use of MOUNJARO has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions (6)]

  . In the pool of placebo-controlled trials in adults, severe gastrointestinal adverse reactions occurred more frequently among patients receiving MOUNJARO (5 mg 1.3%, 10 mg 0.4%, 15 mg 1.2%) than placebo (0.9%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

  MOUNJARO is not recommended in patients with severe gastroparesis.
  )
• Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy:
  Has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Monitor patients with a history of diabetic retinopathy for progression. (
  5.7 Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy

  Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. MOUNJARO has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
  )
• Acute Gallbladder Disease:
  Has occurred in clinical trials. If cholelithiasis is suspected, gallbladder studies and clinical follow-up are indicated. (
  5.8 Acute Gallbladder Disease

  Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing.

  In MOUNJARO placebo-controlled clinical trials in adults, acute gallbladder disease (cholelithiasis, biliary colic, and cholecystectomy) was reported by 0.6% of MOUNJARO-treated patients and 0% of placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.
  )
• Pulmonary Aspiration During General Anesthesia or Deep Sedation:
  Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. (
  5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation

  MOUNJARO delays gastric emptying

  [see Clinical Pharmacology (12.2)]

  . There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

  Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking MOUNJARO, including whether modifying preoperative fasting recommendations or temporarily discontinuing MOUNJARO could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking MOUNJARO.
  )

The following serious adverse reactions are described below or elsewhere in the prescribing information:

• Risk of Thyroid C-cell Tumors
  [see Warnings and Precautions (

  5.1 Risk of Thyroid C-Cell Tumors

  In both sexes of rats, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in a 2-year study at clinically relevant plasma exposures

  [see Nonclinical Toxicology (13.1)]

  . It is unknown whether MOUNJARO causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

  MOUNJARO is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of MOUNJARO and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).

  Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with MOUNJARO. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

  )]
• Acute Pancreatitis
  [see Warnings and Precautions (

  5.2 Acute Pancreatitis

  Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, or MOUNJARO

  [see Adverse Reactions (6)]

  .

  After initiation of MOUNJARO, observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back) and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue MOUNJARO and initiate appropriate management.

  )]
• Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
  [see Warnings and Precautions (

  5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

  Patients receiving MOUNJARO in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia

  [see Adverse Reactions (6.1), Drug Interactions (7.1)]

  .

  The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

  )]
• Hypersensitivity Reactions
  [see Warnings and Precautions (

  5.4 Hypersensitivity Reactions

  Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with MOUNJARO. If hypersensitivity reactions occur, discontinue use of MOUNJARO; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous serious hypersensitivity reaction to tirzepatide or any of the excipients in MOUNJARO

  [see Contraindications (4), Adverse Reactions (6.2)]

  .

  Anaphylaxis and angioedema have been reported with GLP-1 receptor agonists. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with MOUNJARO.

  )]
• Acute Kidney Injury Due to Volume Depletion
  [see Warnings and Precautions (

  5.5 Acute Kidney Injury Due to Volume Depletion

  There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, or MOUNJARO. The majority of the reported events occurred in patients who experienced gastrointestinal adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea

  [see Adverse Reactions (6)]

  .

  Monitor renal function in patients reporting adverse reactions to MOUNJARO that could lead to volume depletion, especially during dosage initiation and escalation of MOUNJARO.

  )]
• Severe Gastrointestinal Adverse Reactions
  [see Warnings and Precautions (

  5.6 Severe Gastrointestinal Adverse Reactions

  Use of MOUNJARO has been associated with gastrointestinal adverse reactions, sometimes severe

  [see Adverse Reactions (6)]

  . In the pool of placebo-controlled trials in adults, severe gastrointestinal adverse reactions occurred more frequently among patients receiving MOUNJARO (5 mg 1.3%, 10 mg 0.4%, 15 mg 1.2%) than placebo (0.9%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

  MOUNJARO is not recommended in patients with severe gastroparesis.

  )]
• Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy
  [see Warnings and Precautions (

  5.7 Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy

  Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. MOUNJARO has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.

  )]
• Acute Gallbladder Disease
  [see Warnings and Precautions (

  5.8 Acute Gallbladder Disease

  Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing.

  In MOUNJARO placebo-controlled clinical trials in adults, acute gallbladder disease (cholelithiasis, biliary colic, and cholecystectomy) was reported by 0.6% of MOUNJARO-treated patients and 0% of placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

  )]
• Pulmonary Aspiration During General Anesthesia or Deep Sedation
  [see Warnings and Precautions (

  5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation

  MOUNJARO delays gastric emptying

  [see Clinical Pharmacology (12.2)]

  . There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

  Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking MOUNJARO, including whether modifying preoperative fasting recommendations or temporarily discontinuing MOUNJARO could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking MOUNJARO.

  )]

MOUNJARO delays gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. (

MOUNJARO (tirzepatide) injection, for subcutaneous use, contains tirzepatide, a once weekly GIP receptor and GLP-1 receptor agonist. Tirzepatide is based on the GIP sequence and contains aminoisobutyric acid (Aib) in positions 2 and 13, a C-terminal amide, and Lys residue at position 20 that is attached to 1,20-eicosanedioic acid via a linker. The molecular weight is 4813.53 Da and the empirical formula is C₂₂₅H₃₄₈N₄₈O₆₈.

Structural formula:

MOUNJARO is a clear, colorless to slightly yellow, sterile, preservative-free solution for subcutaneous use. Each single-dose pen or single-dose vial contains a 0.5 mL solution of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide and the following excipients: sodium chloride (4.1 mg), sodium phosphate dibasic heptahydrate (0.7 mg), and water for injection. Hydrochloric acid solution and/or sodium hydroxide solution may have been added to adjust the pH. MOUNJARO has a pH of 6.5 – 7.5.

Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It is an amino-acid sequence including a C20 fatty diacid that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1.

Tirzepatide enhances first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner.

A 2-year carcinogenicity study was conducted with tirzepatide in male and female rats at doses of 0.15, 0.50, and 1.5 mg/kg (0.1-, 0.4-, and 1-fold the MRHD of 15 mg once weekly based on AUC) administered by subcutaneous injection twice weekly. A statistically significant increase in thyroid C-cell adenomas was observed in males (≥0.5 mg/kg) and females (≥0.15 mg/kg), and a statistically significant increase in thyroid C-cell adenomas and carcinomas combined was observed in males and females at all doses examined. In a 6-month carcinogenicity study in rasH2 transgenic mice, tirzepatide at doses of 1, 3, and 10 mg/kg administered by subcutaneous injection twice weekly was not tumorigenic.

Tirzepatide was not genotoxic in a rat bone marrow micronucleus assay.

In fertility and early embryonic development studies, male and female rats were administered twice weekly subcutaneous doses of 0.5, 1.5, or 3 mg/kg (0.3-, 1-, and 2-fold and 0.3-, 0.9-, and 2-fold, respectively, the MRHD of 15 mg once weekly based on AUC). No effects of tirzepatide were observed on sperm morphology, mating, fertility, and conception. In female rats, an increase in the number of females with prolonged diestrus and a decrease in the mean number of corpora lutea resulting in a decrease in the mean number of implantation sites and viable embryos was observed at all dose levels. These effects were considered secondary to the pharmacological effects of tirzepatide on food consumption and body weight.

The effectiveness of MOUNJARO as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus was established in five trials. In these trials, MOUNJARO was studied as monotherapy (SURPASS-1); as an add-on to metformin, sulfonylureas, and/or sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) (SURPASS-2, -3, and -4); and in combination with basal insulin with or without metformin (SURPASS-5). In these trials, MOUNJARO (5 mg, 10 mg, and 15 mg given subcutaneously once weekly) was compared with placebo, semaglutide 1 mg, insulin degludec, and/or insulin glargine

[see Clinical Studies (

14.2 Monotherapy Use of MOUNJARO in Adult Patients with Type 2 Diabetes Mellitus

SURPASS-1 (NCT03954834) was a 40-week double-blind trial that randomized 478 adult patients with type 2 diabetes mellitus with inadequate glycemic control with diet and exercise to subcutaneous MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg, or placebo once weekly.

Patients had a mean age of 54 years, and 52% were men. The mean duration of type 2 diabetes mellitus was 4.7 years, and the mean BMI was 32 kg/m². Overall, 36% were White, 35% were Asian, 25% were American Indians/Alaska Natives, and 5% were Black or African American; 43% identified as Hispanic or Latino ethnicity.

Monotherapy with MOUNJARO 5 mg, 10 mg and 15 mg once weekly for 40 weeks resulted in a statistically significant reduction in HbA1c compared with placebo (seeTable 4).

Table 4: Results at Week 40 in a Trial of MOUNJARO as Monotherapy in Adult Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control with Diet and Exercise

aThe modified intent-to-treat population consists of all randomly assigned participants who were exposed to at least 1 dose of study drug. Patients who discontinued study treatment because they did not meet study enrollment criteria were excluded. During the trial, rescue medication (additional antihyperglycemic medication) was initiated by 25%, 2%, 3%, and 2% of patients randomized to placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. At Week 40 the HbA1c data were missing for 12%, 6%, 7%, and 14% of patients randomized to placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Missing Week 40 data were imputed using placebo-based multiple imputation.
bLeast-squares mean from ANCOVA adjusted for baseline value and other stratification factors.
cp<0.001 (two-sided) for superiority versus placebo, adjusted for multiplicity.
dAnalyzed using logistic regression adjusted for baseline value and other stratification factors.
	Placebo	MOUNJARO 5 mg	MOUNJARO 10 mg	MOUNJARO 15 mg
Modified Intent-to-Treat (mITT) Population (N)a	113	121	121	120
HbA1c (%)
Baseline (mean)	8.1	8.0	7.9	7.9
Change at Week 40b	-0.1	-1.8	-1.7	-1.7
Difference from placebob(95% CI)	--	-1.7c (-2.0, -1.4)	-1.6c (-1.9, -1.3)	-1.6c (-1.9, -1.3)
Patients (%) achieving HbA1c <7%d	23	82c	85c	78c
Fasting Serum Glucose (mg/dL)
Baseline (mean)	155	154	153	154
Change at Week 40b	4	-40	-40	-39
Difference from placebob(95% CI)	--	-43c (-55, -32)	-43c (-55, -32)	-42c (-54, -30)
Body Weight (kg)
Baseline (mean)	84.5	87.0	86.2	85.5
Change at Week 40b	-1.0	-6.3	-7.0	-7.8
Difference from placebob(95% CI)	--	-5.3c (-6.8, -3.9)	-6.0c (-7.4, -4.6)	-6.8c (-8.3, -5.4)

,

14.3 MOUNJARO Use in Combination with Metformin, Sulfonylureas, and/or SGLT2 Inhibitors in Adult Patients with Type 2 Diabetes Mellitus

Add-on to metformin

SURPASS-2 (NCT03987919) was a 40-week open-label trial (double-blind with respect to MOUNJARO dose assignment) that randomized 1879 adult patients with type 2 diabetes mellitus with inadequate glycemic control on stable doses of metformin alone to the addition of subcutaneous MOUNJARO 5 mg, MOUNJARO 10 mg, or MOUNJARO 15 mg once weekly or subcutaneous semaglutide 1 mg once weekly.

Patients had a mean age of 57 years and 47% were men. The mean duration of type 2 diabetes mellitus was 8.6 years, and the mean BMI was 34 kg/m². Overall, 83% were White, 4% were Black or African American, and 1% were Asian; 70% identified as Hispanic or Latino ethnicity.

Treatment with MOUNJARO 10 mg and 15 mg once weekly for 40 weeks resulted in a statistically significant reduction in HbA1c compared with semaglutide 1 mg once weekly (seeTable 5andFigure 2).

Table 5: Results at Week 40 in a Trial of MOUNJARO versus Semaglutide 1 mg in Adult Patients with Type 2 Diabetes Mellitus Added to Metformin

aThe modified intent-to-treat population consists of all randomly assigned participants who were exposed to at least 1 dose of study drug. Patients who discontinued study treatment because they did not meet study enrollment criteria were excluded. During the trial, rescue medication (additional antihyperglycemic medication) was initiated by 3%, 2%, 1%, and 1% of patients randomized to semaglutide 1 mg, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. At Week 40 the HbA1c endpoint was missing for 5%, 4%, 5%, and 5% of patients randomized to semaglutide 1 mg, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Missing Week 40 data were imputed using multiple imputation with retrieved dropout.
bLeast-squares mean from ANCOVA adjusted for baseline value and other stratification factors.
cp<0.05 (two-sided) for superiority versus semaglutide, adjusted for multiplicity.
dp<0.001 (two-sided) for superiority versus semaglutide, adjusted for multiplicity.
eAnalyzed using logistic regression adjusted for baseline value and other stratification factors.
fp<0.01 (two-sided) for superiority versus semaglutide, adjusted for multiplicity.
	Semaglutide 1 mg	MOUNJARO 5 mg	MOUNJARO 10 mg	MOUNJARO 15 mg
Modified Intent-to-Treat (mITT) Population (N) a	468	470	469	469
HbA1c (%)
Baseline (mean)	8.3	8.3	8.3	8.3
Change at Week 40b	-1.9	-2.0	-2.2	-2.3
Difference from semaglutideb(95% CI)	--	-0.2c (-0.3, -0.0)	-0.4d (-0.5, -0.3)	-0.5d (-0.6, -0.3)
Patients (%) achieving HbA1c <7%e	79	82	86f	86f
Fasting Serum Glucose (mg/dL)
Baseline (mean)	171	174	174	172
Change at Week 40b	-49	-55	-59	-60
Body Weight (kg)
Baseline (mean)	93.7	92.5	94.8	93.8
Change at Week 40b	-5.7	-7.6	-9.3	-11.2
Difference from semaglutideb(95% CI)	--	-1.9c (-2.8, -1.0)	-3.6d (-4.5, -2.7)	-5.5d (-6.4, -4.6)

Figure 2: Mean HbA1c (%) Over Time - Baseline to Week 40

Number of patients
MOUNJARO 5mg	470									451	470
MOUNJARO 10mg	469									445	469
MOUNJARO 15mg	469									447	469
Semaglutide 1mg	468									443	468

Note: Displayed results are from modified Intent-to-Treat Full Analysis Set. (1) Observed mean value from Week 0 to Week 40, and (2) least-squares mean ± standard error at Week 40 multiple imputation (MI).

Add-on to metformin with or without SGLT2 inhibitor

SURPASS-3 (NCT03882970) was a 52-week open-label trial that randomized 1444 adult patients with type 2 diabetes mellitus with inadequate glycemic control on stable doses of metformin with or without SGLT2 inhibitor to the addition of subcutaneous MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg once weekly, or insulin degludec 100 units/mL once daily. In this trial, 32% of patients were on SGLT2 inhibitor. Insulin degludec was initiated at 10 units once daily and adjusted weekly throughout the trial using a treat-to-target algorithm based on self-measured fasting blood glucose values. At Week 52, 26% of patients randomized to insulin degludec achieved the fasting serum glucose target of <90 mg/dL, and the mean daily insulin degludec dose was 49 U (0.5 U per kilogram).

Patients had a mean age of 57 years, and 56% were men. The mean duration of type 2 diabetes mellitus was 8.4 years, and the mean baseline BMI was 34 kg/m². Overall, 91% were White, 3% were Black or African American, and 5% were Asian; 29% identified as Hispanic or Latino ethnicity.

Treatment with MOUNJARO 10 mg and 15 mg once weekly for 52 weeks resulted in a statistically significant reduction in HbA1c compared with daily insulin degludec (seeTable 6).

Table 6: Results at Week 52 in a Trial of MOUNJARO versus Insulin Degludec in Adult Patients with Type 2 Diabetes Mellitus Added to Metformin with or without SGLT2 Inhibitor

aThe modified intent-to-treat population consists of all randomly assigned participants who were exposed to at least 1 dose of study drug. Patients who discontinued study treatment because they did not meet study enrollment criteria were excluded. During the trial, rescue medication (additional antihyperglycemic medication) was initiated by 1%,1%, 1%, and 2% of patients randomized to insulin degludec, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. At Week 52 the HbA1c endpoint was missing for 9%, 6%, 10%, and 5% of patients randomized to insulin degludec, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Missing Week 52 data were imputed using multiple imputation with retrieved dropout.
bLeast-squares mean from ANCOVA adjusted for baseline value and other stratification factors.
cp<0.001 (two-sided) for superiority versus insulin degludec, adjusted for multiplicity.
dAnalyzed using logistic regression adjusted for baseline value and other stratification factors.
	Insulin Degludec	MOUNJARO 5 mg	MOUNJARO 10 mg	MOUNJARO 15 mg
Modified Intent-to-Treat (mITT)aPopulation (N)	359	358	360	358
HbA1c (%)
Baseline (mean)	8.1	8.2	8.2	8.2
Change at Week 52b	-1.3	-1.9	-2.0	-2.1
Difference from insulin degludecb(95% CI)	--	-0.6c (-0.7, -0.5)	-0.8c (-0.9, -0.6)	-0.9c (-1.0, -0.7)
Patients (%) achieving HbA1c <7%d	58	79c	82c	83c
Fasting Serum Glucose (mg/dL)
Baseline (mean)	167	172	170	168
Change at Week 52b	-51	-47	-50	-54
Body Weight (kg)
Baseline (mean)	94.0	94.4	93.8	94.9
Change at Week 52b	1.9	-7.0	-9.6	-11.3
Difference from insulin degludecb(95% CI)	--	-8.9c (-10.0, -7.8)	-11.5c (-12.6, -10.4)	-13.2c (-14.3, -12.1)

Add-on to 1-3 oral anti-hyperglycemic agents (metformin, sulfonylurea, or SGLT-2 inhibitor)

SURPASS-4 (NCT03730662) was a 104-week open-label trial (52-week primary endpoint) that randomized 2002 adult patients with type 2 diabetes mellitus with increased cardiovascular risk to subcutaneous MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg once weekly, or insulin glargine 100 units/mL once daily (1:1:1:3 ratio) on a background of metformin (95%) and/or sulfonylureas (54%) and/or SGLT2 inhibitors (25%).

Patients had a mean age of 64 years, and 63% were men. The mean duration of type 2 diabetes mellitus was 11.8 years, and the mean baseline BMI was 33 kg/m². Overall, 82% were White, 4% were Black or African American, and 4% were Asian; 48% identified as Hispanic or Latino ethnicity. Across all treatment groups, 87% had a history of cardiovascular disease. At baseline, eGFR was ≥90 mL/min/1.73 m²in 43%, 60 to 90 mL/min/1.73 m²in 40%, 45 to 60 mL/min/1.73 m²in 10%, and 30 to 45 mL/min/1.73 m²in 6% of patients.

Insulin glargine was initiated at 10 U once daily and adjusted weekly throughout the trial using a treat-to-target algorithm based on self-measured fasting blood glucose values. At Week 52, 30% of patients randomized to insulin glargine achieved the fasting serum glucose target of <100 mg/dL, and the mean daily insulin glargine dose was 44 U (0.5 U per kilogram).

Treatment with MOUNJARO 10 mg and 15 mg once weekly for 52 weeks resulted in a statistically significant reduction in HbA1c compared with insulin glargine once daily (seeTable 7).

Table 7: Results at Week 52 in a Trial of MOUNJARO versus Insulin Glargine in Adult Patients with Type 2 Diabetes Mellitus Added to Metformin and/or Sulfonylurea and/or SGLT2 Inhibitor

aThe modified intent-to-treat population consists of all randomly assigned participants who were exposed to at least 1 dose of study drug. Patients who discontinued study treatment because they did not meet study enrollment criteria were excluded. During the trial, rescue medication (additional antihyperglycemic medication) was initiated by 1%, 0%, 0%, and 1% of patients randomized to insulin glargine, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. At Week 52 the HbA1c endpoint was missing for 9%, 9%, 6%, and 4% of patients randomized to insulin glargine, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Missing Week 52 data were imputed using multiple imputation with retrieved dropout.
bLeast-squares mean from ANCOVA adjusted for baseline value and other stratification factors.
cp<0.001 (two-sided) for superiority versus insulin glargine, adjusted for multiplicity.
dAnalyzed using logistic regression adjusted for baseline value and other stratification factors.
	Insulin Glargine	MOUNJARO 5 mg	MOUNJARO 10 mg	MOUNJARO 15 mg
Modified Intent-to-Treat (mITT) Population (N)a	998	328	326	337
HbA1c (%)
Baseline (mean)	8.5	8.5	8.6	8.5
Change at Week 52b	-1.4	-2.1	-2.3	-2.4
Difference from insulin glargineb(95% CI)	--	-0.7c (-0.9, -0.6)	-0.9c (-1.1, -0.8)	-1.0c (-1.2, -0.9)
Patients (%) achieving HbA1c <7%d	49	75c	83c	85c
Fasting Serum Glucose (mg/dL)
Baseline (mean)	168	172	176	174
Change at Week 52b	-49	-44	-50	-55
Body Weight (kg)
Baseline (mean)	90.2	90.3	90.6	90.0
Change at Week 52b	1.7	-6.4	-8.9	-10.6
Difference from insulin glargineb(95% CI)	--	-8.1c (-8.9, -7.3)	-10.6c (-11.4, -9.8)	-12.2c (-13.0, -11.5)

,

14.4 MOUNJARO Use in Combination with Basal Insulin with or without Metformin in Adult Patients with Type 2 Diabetes Mellitus

SURPASS-5 (NCT04039503) was a 40-week double-blind trial that randomized 475 adult patients with type 2 diabetes mellitus with inadequate glycemic control on insulin glargine 100 units/mL, with or without metformin, to subcutaneous MOUNJARO 5 mg, MOUNJARO 10 mg, MOUNJARO 15 mg once weekly, or placebo. The dose of background insulin glargine was adjusted using a treat-to-target algorithm based on self-measured fasting blood glucose values, targeting <100 mg/dL.

Patients had a mean age of 61 years, and 56% were men. The mean duration of type 2 diabetes mellitus was 13.3 years, and the mean baseline BMI was 33 kg/m². Overall, 80% were White, 1% were Black or African American, and 18% were Asian; 5% identified as Hispanic or Latino ethnicity.

The mean dose of insulin glargine at baseline was 34, 32, 35, and 33 units/day for patients receiving MOUNJARO 5 mg, 10 mg, 15 mg, and placebo, respectively. At randomization, the initial insulin glargine dose in patients with HbA1c ≤8.0% was reduced by 20%. At week 40, mean dose of insulin glargine was 38, 36, 29, and 59 units/day for patients receiving MOUNJARO 5 mg, 10 mg, 15 mg, and placebo, respectively.

Treatment with MOUNJARO 5 mg once weekly, 10 mg once weekly and 15 mg once weekly for 40 weeks resulted in a statistically significant reduction in HbA1c compared with placebo (seeTable 8).

Table 8: Results at Week 40 in a Trial of MOUNJARO Added to Basal Insulin with or without Metformin in Adult Patients with Type 2 Diabetes Mellitus

aThe modified intent-to-treat population consists of all randomly assigned participants who were exposed to at least 1 dose of study drug. Patients who discontinued study treatment because they did not meet study enrollment criteria were excluded. During the trial, rescue medication (additional antihyperglycemic medication) was initiated by 4%, 1%, 0%, and 1% of patients randomized to placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. At Week 40 the HbA1c endpoint was missing for 2%, 6%, 3%, and 7% of patients randomized to placebo, MOUNJARO 5 mg, 10 mg, and 15 mg, respectively. Missing Week 40 data were imputed using placebo-based multiple imputation.
bLeast-squares mean from ANCOVA adjusted for baseline value and other stratification factors.
cp<0.001 (two-sided) for superiority versus placebo, adjusted for multiplicity.
dAnalyzed using logistic regression adjusted for baseline value and other stratification factors.
	Placebo	MOUNJARO 5 mg	MOUNJARO 10 mg	MOUNJARO 15 mg
Modified Intent-to-Treat (mITT) Population (N)a	119	116	118	118
HbA1c (%)
Baseline (mean)	8.4	8.3	8.4	8.2
Change at Week 40b	-0.9	-2.1	-2.4	-2.3
Difference from placebob(95% CI)	--	-1.2c (-1.5, -1.0)	-1.5c (-1.8, -1.3)	-1.5c (-1.7, -1.2)
Patients (%) achieving HbA1c <7%d	35	87c	90c	85c
Fasting Serum Glucose (mg/dL)
Baseline (mean)	164	163	163	160
Change at Week 40b	-39	-58	-64	-63
Difference from placebob(95% CI)	--	-19c (-27, -11)	-25c (-32, -17)	-23c (-31, -16)
Body Weight (kg)
Baseline (mean)	94.2	95.8	94.6	96.0
Change at Week 40b	1.6	-5.4	-7.5	-8.8
Difference from placebob(95% CI)	--	-7.1c (-8.7, -5.4)	-9.1c (-10.7, -7.5)	-10.5c (-12.1, -8.8)

)]

In adult patients with type 2 diabetes mellitus, treatment with MOUNJARO produced a statistically significant reduction from baseline in HbA1c compared to placebo. The effectiveness of MOUNJARO was not impacted by age, gender, race, ethnicity, region, or by baseline BMI, HbA1c, diabetes duration, or renal function.

MOUNJARO 5 mg and 10 mg was studied in pediatric patients 10 years of age and older with type 2 diabetes in combination with metformin and/or basal insulin

MOUNJARO is a clear, colorless to slightly yellow solution available in cartons containing 4 pre-filled single-dose pens or 1 single-dose vial as follows:

Talk to your healthcare provider about how to inject MOUNJARO the right way.

• MOUNJARO is a single-dose vial.
• MOUNJARO is used 1 time each week.
• Inject under the skin (subcutaneously) only.
• You or another person may inject into your stomach (abdomen) or thigh.
• Another person can inject into the back of your upper arm.

• 1 single-dose MOUNJARO vial
• 1 syringe and 1 needle, supplied separately (for example, use a 1 mL syringe and needle as recommended by your healthcare provider)
• 1 alcohol swab
• gauze
• 1 sharps container for throwing away used needles and syringes.
  See
  “Disposing of used needles and syringes” at the end of these instructions.

Guide to parts Vial	Needle and Syringe (not included)

Make sure the medicine:

Step 1: Pull off the plastic protective cap. Do not remove the rubber stopper.
Step 2: Wipe the rubber stopper with an alcohol swab.
Step 3: Remove the outer wrapping from the syringe.
Step 4: Remove the outer wrapping from the needle. The syringe that your healthcare provider recommended may have a pre-attached needle. If the needle is attached, skip to step 6.
Step 5: Place the needle on top of the syringe and turn until it is tight and firmly attached.
Step 6: Remove the needle shield by pulling straight off.
Step 7: Hold the syringe in one hand with the needle pointing up. With the other hand pull down on the plunger until the plunger tip reaches the line on the syringe indicating that 0.5 mL of air has been drawn into the syringe.
Step 8: Push the needle through the rubber stopper of the vial.
Step 9: Push the plunger all the way in. This puts air into the vial and makes it easier to pull the solution from the vial.
Step 10: Turn the vial and syringe upside down. Make sure that the tip of the needle is in the liquid and slowly pull the plunger down until the plunger tip is past the 0.5 mL line. If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top.
Step 11: Slowly push the plunger up until the plunger tip reaches the 0.5 mL line.
Step 12: Pull the syringe out of the rubber stopper of the vial.

• Inject exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you should pinch the skin before injecting.
• Change (rotate) your injection site within the area you choose for each dose
  to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.
• Do not
  inject where the skin has pits, is thickened, or has lumps.
• Do not
  inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.
• Do not
  mix MOUNJARO with any other medicine.
• Do not
  inject MOUNJARO in the same injection site used for other medicines.

Step 13: Choose your injection site. You can inject MOUNJARO under the skin (subcutaneously) of your stomach area (abdomen) or thighs. Someone else can inject in your stomach area, thighs, or the back of the upper arms.
Step 14: Insert the needle into your skin.
Step 15: Push down on the plunger to inject your dose. The needle should stay in your skin for at least 5 seconds to make sure you have injected all of your dose.
Step 16: Pull the needle out of your skin. If you see blood after you take the needle out of your skin, press the injection site with a piece of gauze or an alcohol swab. Do not rub the area. Do not recap the needle. Recapping the needle can lead to a needle stick injury.

• Put your used needle and syringe in an FDA-cleared sharps disposal container right away after use.
  Do not
  throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  
  • - made of a heavy-duty plastic,
  • - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • - upright and stable during use,
  • - leak-resistant, and
  • - properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at:
  
  http://www.fda.gov/safesharpsdisposal.
• Do not
  dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.
  Do not
  recycle your used sharps disposal container.

• Store all unopened vials in the refrigerator at 36°F to 46°F (2°C to 8°C).
• You may store the unopened vial at room temperature up to 86°F (30°C) for up to 21 days.
• Do not
  freeze.
  Do not
  use if MOUNJARO has been frozen.
• Store the vial in the original carton to protect from light.
• Throw away all opened vials after use, even if there is medicine left in the vial.

If you have any questions or problems with your MOUNJARO, contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare provider for help.

MOUNJARO is a registered trademark of Eli Lilly and Company.

Copyright © 2023, 2024, Eli Lilly and Company. All rights reserved.

MON-VL-0002-IFU-20240229

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: February 2024

Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It is an amino-acid sequence including a C20 fatty diacid that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1.

Tirzepatide enhances first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner.