TIRZEPATIDE INJECTION
Clinical Criteria Summary
Document 550: MON Tirzepatide ZEPBOUND Monograph Dec 2023
Indication & Patient Selection
- • Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults.
- • Requires an initial body mass index (BMI) of ≥30 kg/m² (obesity) or ≥27 kg/m² (overweight) with at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).
Dosing & Administration
- • Administered subcutaneously once weekly.
- • Initial dose is 2.5 mg/0.5 mL.
- • Weekly dose should be increased by 2.5 mg at 4-week intervals.
- • Maintenance doses are 5 mg, 10 mg, and 15 mg SC once weekly.
- • Maximum dose is 15 mg SC once weekly.
Contraindications
- • Personal or family history of medullary thyroid carcinoma (MTC).
- • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- • Known serious hypersensitivity to tirzepatide or any excipients in ZEPBOUND.
Warnings & Precautions / Monitoring Criteria
- • Pancreatitis: Discontinue promptly if pancreatitis is suspected.
- • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Concomitant use may increase the risk of severe hypoglycemia; reducing dose of insulin secretagogue or insulin may be necessary.
- • Hypersensitivity Reactions: Discontinue tirzepatide if suspected.
- • Acute Kidney Injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions that could lead to volume depletion.
- • Severe Gastrointestinal Disease: Not recommended in patients with severe gastrointestinal disease.
- • Diabetic Retinopathy Complications: Monitor patients with a history of diabetic retinopathy for progression; not studied in non-proliferative requiring acute therapy, proliferative, or diabetic macular edema.
- • Acute Gallbladder Disease: If cholelithiasis is suspected, perform gallbladder studies and clinical follow-up.
- • Suicide Behavior and Ideation: Avoid use in patients with a history of suicidal attempts or active suicidal ideation. Monitor for emergence or worsening of depression, suicidal thoughts/behaviors, or unusual changes in mood/behavior; discontinue if experienced.
Special Populations
- • Pregnancy/Fetal Harm: Discontinue when pregnancy is recognized. Weight loss offers no benefit to a pregnant patient and may cause fetal harm.
- • Reproductive Potential: Patients using oral contraceptives should switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiating tirzepatide and for 4 weeks after each dose escalation due to delayed gastric emptying.
Document 551: Tirzepatide ZEPBOUND for weight management CFU
Exclusion Criteria
- Known pregnancy
- Lactating status
- Type 1 diabetes (exception: may be considered under careful supervision if followed by a diabetes/weight management specialist)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (excludes patients with a known cause that no longer presents a risk)
- Known proliferative diabetic retinopathy (PDR), severe non-proliferative diabetic retinopathy (NPDR), clinically significant macular edema (ME), or diabetic macular edema (DME) unless risks/benefits are discussed, documented in the EHR with monitoring plans/follow-up, and an eye specialist is informed at initiation
Inclusion Criteria
- Documented participation in a comprehensive lifestyle intervention (CLI) targeting diet, physical activity, and behavioral changes within the past year
- Body Mass Index (BMI) ≥ 27 kg/m² with at least one weight-related comorbidity
- Weight-related comorbidities include: hypertension, type 2 diabetes, prediabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease, heart failure with preserved ejection fraction, previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease
- Discontinuation of medications that may precipitate weight gain should be considered if clinically appropriate
Additional Inclusion Criteria (Females Who Can Become Pregnant)
- Pregnancy must be excluded prior to receiving tirzepatide
- Contraceptive counseling regarding potential risks vs. benefits of pregnancy during therapy is required
- Females of childbearing potential using oral contraceptives must be counseled to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and 4 weeks after each dose escalation
Monitoring & Clinical Management Requirements
- For patients with diabetes, diabetic eye exam results should be available within the past 12 months (or 24 months if no evidence of retinopathy)
- Patients with a history of diabetic retinopathy require planned follow-up with an eye provider to monitor progression; consultation with an eye care specialist is required for any concerns
- Pancreatitis risk factors include triglyceride level > 1000 mg/dL, known gallstones with intact gallbladder, and high alcohol intake
Document 421: Weight Management Medications Clinical Recommendations
Criteria for General Weight Management & Shared Requirements
- BMI > 30 kg/m² or BMI > 27 kg/m² with obesity-related conditions
- Must be prescribed in conjunction with a comprehensive lifestyle intervention (CLI)
- Clinically meaningful weight loss is generally considered approximately a 5% reduction from baseline body weight
- WMMs should be viewed as chronic therapy; discontinuation is commonly associated with weight regain
- Shared decision-making required considering efficacy, adverse effects, contraindications and warnings, comorbidities, patient preferences, cost, and applicable CFU
- Review current treatment regimen for medications that may contribute to weight gain and consider alternative therapy when appropriate
Criteria for Comprehensive Lifestyle Intervention (CLI) Participation
- Documentation of participation in CLI within the past year on at least one occasion is required for eligibility
- CLI must target all three aspects of weight management: diet, physical activity, and behavioral changes
- Self-management tools without clinician contact do not meet the definition of CLI
- Routine lifestyle education/coaching without a standardized curriculum delivered over a series of sessions does not meet the definition of CLI
- Programs targeting only one or two aspects of weight management do not meet the definition of CLI
Criteria for Naltrexone/Bupropion
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; twice daily
- Avoid/Contraindications: Pregnancy, Lactation, Seizure disorder, Eating disorders, Uncontrolled hypertension, Chronic opioid use or acute opioid withdrawal, MAOI use within 14 days
- Post-Marketing Considerations: Type 2 diabetes
- Monitoring & Safety: Monitor blood pressure, heart rate, and mood; Precautions include suicidal behavior and ideation [Boxed Warning]
- Common ADRs: Nausea, constipation, acute headache, vomiting, dizziness, insomnia, dry mouth, diarrhea, anxiety
Criteria for Orlistat
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; three times daily with meals
- Avoid/Contraindications: Pregnancy, Lactation, Chronic malabsorption syndrome, Cholestasis
- Post-Marketing Considerations: Prediabetes, Type 2 diabetes, BP lowering
- Monitoring & Safety: Monitor hepatotoxicity; Precautions include fat-soluble vitamin deficiency and oxalate nephropathy
- Common ADRs: Oily spotting/stools, fecal urgency, flatulence
Criteria for Phentermine/Topiramate
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; once daily
- Avoid/Contraindications: Pregnancy, Lactation, Glaucoma, Hyperthyroidism, MAOI use within 14 days
- Post-Marketing Considerations: Prediabetes, Type 2 diabetes, BP lowering
- Monitoring & Safety: Monitor heart rate, blood pressure, and mood changes; Precautions include fetal toxicity (REMS), nephrolithiasis risk, and seizure risk with abrupt discontinuation
- Common ADRs: Paraesthesias, dysgeusia, insomnia, constipation, dry mouth
Criteria for Semaglutide (Injection and Oral)
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once weekly (injection) / Oral; once daily on an empty stomach with up to 4 ounces of water (tablet); Eating, drinking, and taking other medications must be avoided for 30 minutes (oral)
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes
- Monitoring & Safety: Monitor risk of worsening diabetic retinopathy in patients with T2DM; Precautions include gallbladder disease and pancreatitis; Avoid concurrent use of a DPP-4 inhibitor due to lack of efficacy
- Common ADRs: GI adverse effects (nausea, diarrhea, constipation, vomiting, abdominal pain), dyspepsia
- FDA-Approved Indications: MASH, Reduction of MACE, Type 2 diabetes (under different brand and doses)
- Post-Marketing Evidence: Prediabetes, HFpEF, Osteoarthritis
Criteria for Liraglutide
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once daily
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes
- Monitoring & Safety: Precautions include gallbladder disease and pancreatitis
- Common ADRs: GI adverse effects (nausea, diarrhea, constipation, vomiting, abdominal pain), dyspepsia
- FDA-Approved Indications: Type 2 diabetes (under different doses), Reduction of MACE (in T2D)
- Post-Marketing Evidence: Prediabetes, Reduction of MASH
Criteria for Tirzepatide
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once weekly
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes, BP lowering
- Monitoring & Safety: Monitor risk of worsening diabetic retinopathy in patients with T2DM; Precautions include gallbladder disease and pancreatitis; Avoid concurrent use of a DPP-4 inhibitor due to lack of efficacy
- FDA-Approved Indications: MASH, Reduction of MACE, Type 2 diabetes (under different brand)
- Post-Marketing Evidence: Prediabetes, BP lowering, HFpEF, Osteoarthritis