TIRZEPATIDE INJ,SOLN
Clinical Criteria Summary
Document 349
Exclusion Criteria
- Diagnosis of Type 1 diabetes
- Personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility including gastroparesis
- History of pancreatitis (does not pertain to patients for whom the cause of pancreatitis is known and no longer presents a risk)
- Pregnancy (insulin generally preferred; use only if potential benefit justifies potential risk to fetus and mother)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits have been discussed with the patient and is documented in the EHR along with monitoring plans and follow-up with an eye specialist who is informed at the time of initiation
Relative Exclusion
- Risk factors for pancreatitis (e.g., untreated fasting triglyceride level > 1000mg/dL, known gallstones with intact gallbladder, alcohol use disorder)
Inclusion Criteria
- Diagnosis of Type 2 diabetes
- Inadequate glycemic control on at least 1mg of semaglutide injection plus two or more glucose lowering drugs (metformin, empagliflozin, insulin, pioglitazone, sulfonylurea) for at least 6 months
- Change needed to achieve goal A1C is less than 1% (goal based on VA/DoD Diabetes Guidelines)
- Adherent to current diabetes medications as evidenced by a review of prescription refill history during the last 6 months
- Current non-GLP 1A drugs are optimized as appropriate
Additional Inclusion Criteria
- Patients with ASCVD or CKD: Receiving empagliflozin unless unable to use
- Patients of childbearing potential using oral contraceptives: Counseled 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
Additional Clinical Requirements & Restrictions
- Prior GLP 1A trial required: Patients on liraglutide or exenatide must be switched to semaglutide first; patients with semaglutide intolerance should trial another GLP 1A before tirzepatide
- Empagliflozin recommendation: Recommended for overweight patients (BMI greater or equal to 27kg/m2) unless unable to use
- Insulin consideration: Consider insulin at any time prior to using tirzepatide, unless unable to use or otherwise inappropriate
- Combination restrictions: Do not use with GLP-1 agonists or DPP-4 inhibitors; concomitant use with alpha glucosidase inhibitors or meglitinides not recommended due to lack of or insufficient data
- Insulin regimen limitations: No data combining tirzepatide with both basal and prandial insulin (including premixed formulations) or with U500 insulin; concomitant use may be done on a case-by-case basis in consultation with an endocrinologist or diabetes specialist
- Retinopathy monitoring: Provider should have diabetic eye examination results within past 12 months on file; consider disease severity and activity; planned follow-up with eye provider required for progression; consult eye care specialist if concerns arise
Document 364
Indication & Population
- • Adults with type 2 diabetes mellitus
- • Adjunct to diet and exercise to improve glycemic control
Dosage & Administration
- • Available in pre-filled single-dose pens: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg
- • Recommended starting dosage: 2.5 mg injected subcutaneously once weekly
- • After 4 weeks, increase to 5 mg injected subcutaneously once weekly
- • If additional glycemic control is needed, increase in 2.5 mg increments after at least 4 weeks on the current dose
- • Maximum dosage: 15 mg subcutaneously once weekly
- • Administer once weekly at any time of day, with or without meals
- • Inject subcutaneously in the abdomen, thigh, or upper arm
Efficacy & Place in Therapy
- • Considered as an intensification option for patients with type 2 diabetes treated with semaglutide 1 mg or 2 mg in need of additional glycemic control
- • Current diabetes therapy, including diet and exercise, should be optimized as appropriate and adherence to therapy confirmed before considering tirzepatide
- • If not already using, consider adding empagliflozin or insulin if appropriate
Contraindications & Warnings/Precautions
- • Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- • Known serious hypersensitivity to tirzepatide or any excipients
- • Pancreatitis: Discontinue promptly if suspected
- • Hypoglycemia with concomitant use of insulin secretagogues or insulin: Reducing dose of insulin secretagogue or insulin may be necessary
- • Hypersensitivity reactions: Discontinue tirzepatide if suspected
- • Severe gastrointestinal disease: Not recommended; has not been studied in these patients
- • Diabetic retinopathy complications: Has not been studied in non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema; monitor patients with a history of diabetic retinopathy for progression
- • Acute gallbladder disease: If cholelithiasis is suspected, perform gallbladder studies and clinical follow-up
Monitoring & Special Populations
- • Acute kidney injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions
- • Oral hormonal contraceptives: Advise patients to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and for 4 weeks after each dose escalation due to reduced Cmax/AUC and delayed Tmax; non-oral hormonal contraceptives are not affected
- • Pregnancy: Use only if potential benefit justifies potential risk to the fetus; insufficient data on drug-related risk of major birth defects or miscarriage
- • Lactation: No data on presence in milk; consider developmental/health benefits of breastfeeding along with mother’s clinical need and potential adverse effects on the breastfed infant
Document 550
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
Exclusion Criteria
- Known pregnancy
- Lactating
- Type 1 diabetes (unless followed by a diabetes/weight management specialist under careful supervision)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (does not apply if the cause is known and 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 with the patient, documented in the electronic health record (EHR) with monitoring plans and 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
- Body mass index (BMI) ≥ 30 kg/m² with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
Additional Inclusion & Counseling Requirements
- For females who can become pregnant: Pregnancy must be excluded prior to receiving the medication; contraceptive counseling regarding potential risks vs. benefits of pregnancy must be provided
- 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 for 4 weeks after each dose escalation
Clinical Monitoring & Management Considerations
- Consider discontinuing medications that may precipitate weight gain if clinically appropriate
- For patients with diabetes: Diabetic eye exam results should be available within the past 12 months (or 24 months if no evidence of retinopathy); consider disease severity and activity; ensure planned follow-up with an eye provider for those with a history of diabetic retinopathy; consult an eye care specialist if concerns arise regarding use
- Individual cases that are exceptions to exclusion or inclusion criteria should be adjudicated at the local facility according to P&T committee and pharmacy services policy
Document 421
Indications & Eligibility
- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria
- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications
- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals
- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations
- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions
- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements
- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance